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Editorial introductions

Current Opinion in Cardiology was launched in 1985. It is the establishment of new diagnostic criteria within the
part of a successful series of review journals whose unique context of familial disease, and to the establishment of
format is designed to provide a systematic and critical algorithms to identify patients at high risk of sudden
assessment of the literature as presented in the many death.
primary journals. The field of cardiology is divided into
14 sections that are reviewed once a year. Each section is William T. Abraham
assigned a Section Editor, a leading authority in the area,
who identifies the most important topics at that time. William T. Abraham, M.D.,
Here we are pleased to introduce the Section Editors for F.A.C.P., F.A.C.C. is Pro-
this issue. fessor of Internal Medicine
and Chief of the Division of
Cardiovascular Medicine at
Section Editors The Ohio State University
College of Medicine, USA.
William J. McKenna He also serves as Deputy
Director of the Dorothy
Dr William McKenna is Pro- M. Davis Heart and Lung
fessor of Cardiology, at Uni- Research Institute. Dr Abra-
versity College London, UK ham earned his medical
and Clinical Director of The degree from Harvard
Heart Hospital, University Medical School in Boston,
College London Hospitals Massachusetts, following which he completed his resi-
Trust. He was born in Mon- dency in internal medicine and fellowships in cardiology
treal, Canada and completed and heart failure/cardiac transplantation at the Univer-
a Bachelor of Arts Degree at sity of Colorado Health Sciences Center. He previously
Yale University before held faculty appointments at the University of Colorado,
graduating from McGill Uni- the University of Cincinnati, and the University of
versity Medical School. He Kentucky. He is board certified in Internal Medicine
completed Internal Medi- and in Cardiovascular Diseases. Dr Abraham’s research
cine Training in at the Royal interests include the role of the kidney in heart failure,
Victoria Hospital in Montreal and in 1976 moved to the neurohormonal mechanisms in heart failure, sleep dis-
Hammersmith Hospital Royal Postgraduate Medical ordered breathing in heart failure, and clinical drug and
School in London to train in cardiology. In 1988 he took device trials in heart failure and cardiac transplantation.
up a post as Sugden Senior Lecturer in the Division of Dr Abraham has received grants from the National
Cardiological Sciences at St George’s Hospital Medical Institutes of Health, the American College of Cardio-
School and in 1993 was made professor of cardiac medi- logy, and the Aetna Quality Care Foundation and has
cine. In October 2000 he was appointed British Heart participated as Principal Investigator in more than 100
Foundation (BHF) Professor of Molecular Cardiology multicenter clinical drug and device trials. In addition to
and in July 2003 moved to University College London authoring more than 600 original papers, abstracts, book
(UCL) as Professor of Cardiology and was appointed chapters, and review articles, Dr Abraham has co-edited
Clinical Director of The Heart Hospital, University a leading textbook on heart failure entitled Heart Failure:
College London Hospital (UCLH) NHS Trust from A Practical Approach to Treatment. Dr Abraham serves on
September 2004. In August 2008 he was appointed Acting the editorial boards of several major journals including
Director (West) of the Institute of Cardiovascular Congestive Heart Failure and Journal Watch Cardiology. He
Science, UCL/UCLH Trust. His main interests have is also a scientific reviewer for such publications as
been in clinical and basic research of the cardiomyopa- Circulation, the European Heart Journal, and the Journal
thies. His recent work has contributed to the identifi- of the American College of Cardiology. Dr Abraham has been
cation of disease-causing genes in hypertrophic, dilated recognized as one of the ‘‘Best Doctors in America’’ for
and arrhythmogenic right ventricular cardiomyopathy, to six consecutive years.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Editorial introductions

David Feldman Dr Feldman’s research interests include the study of G-

protein coupled receptors, mechanisms of heart failure,
Dr Feldman MD, PhD, genomic-mediated developmental changes and cardiac
FACC, FAHA is the Director transplantation. He is currently funded by multiple
of Heart Failure and Cardiac National Institute of Health grants and the Heart fail-
Transplant at The Ohio State ure Society of America. His research endeavors have
University (OSU), USA. Dr included both basic and clinical research as he has
Feldman is also the director extensive publications in both clinical and basic
of the heart failure fellow- science. Despite his research, Dr Feldman continues
ship program at OSU. He to have a busy clinical practice. His clinical focus is
has appointments in the De- cardiac transplant, end-stage disease management, and
partments of Cardiovascular critical care.
Medicine, Physiology and
Cell Biology as well as in
the school of Pharmacy.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Lamin A/C deficiency as a cause of familial
dilated cardiomyopathy
Rohit Malhotra and Pamela K. Mason
University of Virginia Health System, Charlottesville, Purpose of review
Virginia, USA
Familial dilated cardiomyopathy is an underrecognized form of dilated cardiomyopathy.
Correspondence to Pamela K. Mason, Assistant Lamin A/C deficiency is probably the most common cause of familial dilated
Professor of Medicine, PO Box 800158,
University of Virginia Health System, Charlottesville, cardiomyopathy. This review will focus on the emerging knowledge of epidemiology,
VA 22908-0158, USA diagnosis, and treatment of patients with lamin A/C deficiency, as well as possible
Tel: +1 434 924 2465; fax: +1 434 924 2581;
e-mail: [email protected] disease mechanisms.
Recent findings
Current Opinion in Cardiology 2009,
24:203–208
Screening of patients with dilated cardiomyopathy continues to indicate that lamin A/C
deficiency is a significant cause. Multiple novel mutations have been found, suggesting
that many mutations are limited to individuals or families. It is unknown how
mutations cause the syndrome, although an animal model has shown that lamin A/C
insufficiency causes apoptosis, particularly in the conduction system. Inheritance is
predominantly autosomal dominant, but penetrance is variable. For symptomatic
patients, the course is malignant, with conduction system disease, atrial fibrillation, heart
failure, and sudden cardiac death. The data are contradictory, and currently, there is no
clear marker for when a lamin A/C-deficient patient is at risk for sudden death.
Summary
Lamin A/C deficiency is an important cause of dilated cardiomyopathy, and diagnosis
requires that clinicians have a high index of suspicion. Our knowledge of the
mechanisms, diagnosis, and treatment of lamin A/C deficiency is incomplete. It is clear
that patients with this condition have a malignant course and need to be followed
aggressively.

Keywords
familial dilated cardiomyopathy, lamin A/C deficiency, sudden cardiac death

Curr Opin Cardiol 24:203–208

ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
0268-4705

have hindered the diagnosis of FDC. Identifying patients

Introduction with possible FDC requires there be sufficient family
Dilated cardiomyopathy (DCM) accounts for approxi- history to find that there are at least two first-degree
mately 60% of all cardiomyopathies [1

]. DCM is a family members with IDC. Many patients do not know
major source of morbidity and mortality, causing conges- their family histories or have small families. In addition,
tive heart failure (CHF) and sudden cardiac death (SCD). this disease has variable and age-dependent penetrance
This is a clinically heterogeneous disease and can be even within families [5,7,8,9
,10
]. Patients who have
caused by ischemia, valvular disease, virus exposure, FDC may have other causes of DCM, such as coronary
toxin exposure, or infiltrative disease. When no overt artery disease or valvular heart disease, which confound
cause of DCM is found, it is termed idiopathic dilated the true diagnosis.
cardiomyopathy (IDC).
The challenges in recognizing FDC families clinically
Over the last several decades, it has become increasingly have made identifying culprit genes difficult. Even when
clear that the cause of many ‘idiopathic’ dilated cardio- FDC families are identified, only a small number of
myopathies is genetic. Familial dilated cardiomyopathy patients are available. Most research has evaluated can-
(FDC) is now thought to account for up to 50% of IDC didate genes. More than 20 different genes have been
patients, whereas in the early 1980s the reported inci- identified in patients with FDC (Table 1). These include
dence of FDC was 2–6.5% [2–5]. Most of these cases genes that affect sarcomeric proteins, cytoskeletal
(>90%) are thought to show autosomal dominant inheri- proteins, nuclear proteins, ion channel proteins, and
tance, although X-linked and autosomal recessive forms mitochondria [1

,11,12,13]. Many of these mutations
have been identified [6]. There are many factors that have been found in few patients, and, indeed, may only
0268-4705 ß 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/HCO.0b013e32832a11c6

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 204 Molecular genetics

Table 1 Genes that have been implicated in the development of transcription, cell cycle regulation, cell differentiation,
dilated cardiomyopathy and apoptosis. Recent in-vitro data suggest various
Locus Gene mutations in the gene may each lead to different altera-
1p1-q21 Lamin A/C
tions in protein function [22
]. This could lead to
1q32 Troponin T dramatically different physiologic consequences for
1q42-q43 a-Actinin distinct mutations.
2q31 Titin
2q35 Desmin
3p21 Troponin C
3p22-p25 SCN5A Laminopathies
5q33 d-Sarcoglycan There are over 200 mutations described in LMNA, which
6q22.1 Phospholamban
10q22-q23 Metavinculin can cause over 20 different phenotypes. This constella-
11p11 Myosin-binding protein-C tion of syndromes is known as the laminopathies. It is
11p15 Cardiac muscle LIM protein unknown how the mutations cause the syndromes, and
12p12 SUR2A
12q22 Thymopoietin up to 25% of patients with LMNA mutation may remain
14q12 b-Myosin heavy chain asymptomatic [23]. Many laminopathies have a multi-
15q14 Cardiac actin system phenotype, and virtually all symptomatic patients
15q22 a-Tropomyosin
17q12 Telethonin have some form of cardiac involvement. Emery–Dreifuss
19q13 Troponin I muscular dystrophy causes muscular dystrophy and
Table adapted from [1

,11,12]. DCM. Hutchinson–Gilford progeria syndrome causes
accelerated aging. Other phenotypes cause partial
lipodystrophy or neuropathy. When patients have multi-
account for FDC within single patients or families. system phenotypes, it is easier to recognize a probable
Although up to 50% of patients with IDC may have familial cause for their cardiomyopathy. However, there
FDC by history, a genetic test may identify the cause are a significant number of patients with lamin A/C
in only a small minority of patients. mutation who have only cardiac manifestations. These
patients often remain undiagnosed.
The exception to this is lamin A/C mutation. Lamin A/C
mutations are thought to be the cause in up to 10% of
FDC cases [14]. Multiple different mutations have been Cardiac manifestations of lamin A/C
found in the lamin A/C gene (LMNA) and testing is deficiency
available at several centers. The diagnosis of lamin A/C The earliest cardiac finding in patients with lamin A/C
deficiency denotes important prognostic information deficiency is usually conduction system disease. In a
[8,15–19]. These patients often have a particularly malig- meta-analysis of 299 carriers of a lamin A/C mutation,
nant course and the penetrance for some mutations 18% of patients less than 10 years of age had evidence of
approaches 100% as patients age. In this review, we will delayed intracardiac conduction. In patients over 30 years
focus on the recent advances in the epidemiology, diag- of age, 92% had conduction system disease, with 44%
nosis, and treatment of lamin A/C deficiency as a cause of requiring pacemaker placement [14]. In early stages,
isolated cardiomyopathy. Many of the other mutations patients have a characteristic electrocardiogram with
described above cause concomitant skeletal muscle low amplitude P waves, prolonged PR interval, but a
disease or other forms of cardiomyopathy such as hyper- relatively normal QRS complex (Fig. 1). Patients sub-
trophic cardiomyopathy and will be covered in other sequently develop atrial fibrillation and DCM. A high
sections. incidence of thromboembolic events has been noted in
lamin A/C-deficient patients (30%), but whether this is
related to undiagnosed atrial dysrhythmias or factors
Lamin A and C specific to lamin A/C deficiency is unknown [24

].
Lamin A and C are type V intermediate filament proteins By age 50, over 60% of patients have symptoms of
found in the nuclear membrane or lamina [20,21]. CHF [14].
LMNA is found on chromosome 1q21.2-q21.3. Lamin
A and C are created by alternative splicing. They are A recent animal model of lamin A/C haploinsufficiency
expressed in terminally differentiated somatic cells and has suggested a mechanism for the clinical cardiac find-
found in multiple different tissues, including skeletal ings [25

]. The earliest finding in mice with one abnor-
and cardiac muscle. The protein is composed of a con- mal LMNA allele was programmed cell death of atrio-
served rod domain with a globular head and tail region. ventricular nodal myocytes. Subsequently, the mice
The functions of lamin A and C are incompletely under- developed worsening electrophysiologic disease. Ulti-
stood, but it is thought that they are important in main- mately, the nonconducting myocytes also experienced
taining nuclear architecture, DNA replication, RNA apoptosis, leading to DCM.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Lamin A/C deficiency as a cause of FDC Malhotra and Mason 205

Figure 1 Characteristic electrocardiogram from an asymptomatic patient with lamin A/C deficiency

Conduction system disease is generally the earliest finding in patients with lamin A/C deficiency. Patients demonstrate low amplitude P waves,
prolonged PR intervals, but narrow QRS complexes.

Lamin A/C-deficient patients are at high risk of SCD, tive sports for greater than 10 years and genotype were
probably at significantly higher risk than patients with predictive on multivariate analysis of risk of SCD. In
other forms of DCM [26]. In one Dutch kindred, there contradiction to previous data, those who did not mani-
was a precipitous decline in survival after age 40, and by fest disease did not have clinical events. However, by age
age 65 no family members were alive [27
]. Meune et al. 60, all patients with a mutation manifested disease,
[15] found that, in a small cohort of patients with known indicating 100% penetrance over time.
lamin A/C defects, 42% of patients experienced SCD.
The approximate mean age and mean ejection fraction in
this cohort were 42 years and 58%, indicating that this Genetic screening
group experienced SCD at young age and with relatively Several mutations in LMNA were identified in five
preserved ejection fraction. Other recent studies have families with DCM with conduction system disease by
also found that risk of SCD precedes left ventricular Fatkin et al. in 1999 [19]. The location of the mutation
dysfunction [28
]. Further, in the meta-analysis described within the gene altered the phenotype. Since then,
above, the need for a pacemaker or the presence of a multiple familial studies [23,30

,31
,32
] have identified
pacemaker did not seem to be predictive of SCD [14]. a number of other novel mutations in exons as well as
splicing sites. These mutations generate missense, splice
A more recent study by Pasotti et al. [29

] also found that site, nonsense, and deletion mutations. The recent
patients with lamin A/C defects experienced a malignant genetic study by Parks et al. [30

] of 324 unrelated
course. By examining 94 patients derived from a genetic DCM patients identified 11 novel LMNA mutations.
analysis of 27 families with DCM, they were able to This study identified a prevalence of LMNA mutations
identify risk factors for SCD. Univariate analysis indi- of 5.9% in the FDC and DCM patients evaluated. Several
cated that New York Heart Association class III or IV, family members of the probands enrolled in this study
clinical manifestation of LMNA deficiency, conduction carried pathogenic LMNA mutations without disease
system disease, left ventricular ejection fraction (LVEF) manifestations, demonstrating a variable penetrance of
less than 35%, left ventricular end-diastolic volume more the disease process. In contrast, there were kindreds in
than 180 ml, and history of competitive athleticism were which only some of the family members who had DCM
predictive of death, CHF, heart transplant, or SCD. had LMNA mutations. This study demonstrates the
Multivariate analysis identified only function class III difficulty in developing a screening examination that
or IV and history of competitive sports as independent does not involve sequencing the entire genetic locus
predictors of an event. SCD occurred in 6.3 per 100 for LMNA, including introns. However, novel mutations
person years among affected individuals. Both competi- may not alter protein structure or function, thus

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 206 Molecular genetics

confounding results of these sequencing tests. No repo- implicated as an early warning sign [12]. These findings
sitory to maintain a correlation between identified warrant more frequent and aggressive follow-up.
genetic mutations and clinical manifestations exists.
Of particular concern in the lamin A/C-deficient popu-
Genetic screening is most useful in identified FDC lation is the accelerated risk of SCD. The data are
families. The probands have usually already developed conflicting, but there is evidence that these patients
clinical disease, although some known mutations do have are at risk prior to the development of the usual markers
a more malignant course, which can help with prognosis for SCD that are used for other forms of DCM, particu-
and therapy. Unfortunately, many newly diagnosed lamin larly left ventricular dysfunction and CHF symptoms.
A/C-deficient families are found to have novel mutations. There is currently no clear marker that can be identified
However, identifying a specific genetic mutation within a by physical examination, laboratory work, or imaging
family can be important for family planning and directing study that indicates that a patient with lamin A/C
follow-up for the family members. Family members of deficiency is now at risk for SCD.
probands should undergo genetic counseling. Although
up to 10% of the IDC patients may have lamin A/C MRI has been evaluated as a modality to diagnose sub-
defects, generalized screening of the DCM population is clinical disease in asymptomatic patients with lamin A/C
not performed. There are too many unidentified deficiency [35

,36
,37]. One recent study [35

] evalu-
mutations and comprehensive screening is insensitive ated the use of MRI to diagnose cardiac involvement in
[33]. There are also substantial resource and financial 12 patients with one mutated allele and no disease
barriers to this kind of testing. We are likely many years manifestations. MRI studies demonstrated differences
from being able to comprehensively screen patients in these patients when compared with 14 control patients.
genetically for FDC. There was no single parameter that identified patients at
risk, but an amalgam of parameters calculated from MRI
measurements was different in carriers when compared
Clinical screening with normals, suggesting that MRI may identify patients
Identifying new lamin A/C-deficient families requires a who are predisposed to disease. These patients will need
high index of suspicion. Patients with IDC and at least to be followed up to determine whether they will mani-
one other first-degree relative with IDC should be con- fest symptoms in order to determine the true predictive
sidered for genetic screening. Most patients with lamin capacity of MRI in these patients. Should all of these
A/C deficiency do have conduction system disease as one patients develop conduction system disease or CHF, a
of the first features, and up to 30% of patients with DCM cardiac MRI may predict who will require more aggres-
and conduction system disease are thought to have sive therapy.
lamin A/C deficiency [2–5]. Finally, while lamin A/C
deficiency causes isolated cardiomyopathies, it often
causes DCM in conjunction with other clinical findings, Therapy
particularly skeletal muscle abnormalities. Careful There is little data to guide therapy for patients with
history, physical examination, and laboratory testing in lamin A/C deficiency. Standard medical therapies for
patients can often identify evidence of mild limb-girdle CHF are employed when patients develop left ventri-
muscular dystrophies or neuropathies in them or their cular dysfunction [33]. It is unknown whether these
family members. patients benefit from being started on angiotensin-con-
verting enzyme inhibitors or b-blockers prior to the
At this time, there is no consensus on the frequency development of CHF. It is also unknown whether the
or type of screening that patients with known mutations use of b-blockers will exacerbate or reveal underlying
and no clinical phenotype should undergo. Recommen- conduction system disease. Patients do often progress to
dations have been made to screen family members of end-stage CHF, and transplantation has been described
affected patients every 3–5 years with physical examin- for this population [17].
ation, electrocardiogram, and echocardiogram, but it is
unknown whether the frequency of screening should There is a substantial role for device therapy in this
increase as patients get older, given that penetrance population. Many of these patients will require pace-
increases as patients age [12]. In addition, the particular makers due to severe conduction system disease. The
genotype alters the rate of disease progression and it is optimal timing of implantable cardioverter defibrillator
unknown how this should affect the screening process. (ICD) placement remains undefined. Meune et al. [15]
Several studies have suggested that left ventricular enlar- placed ICDs in 19 patients who had lamin A/C mutations
gement may be one of the earliest findings in asympto- and indications for pacemakers, but had no traditional
matic patients who go on to develop symptomatic FDC indications for ICDs. Eight of these patients (42%)
[4,34]. Left bundle branch block (LBBB) has also been received appropriate shocks. It has been suggested that

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 Lamin A/C deficiency as a cause of FDC Malhotra and Mason 207

the development of conduction system disease may be a 5 Grunig E, Tasman JA, Kucherer H. Frequency and phenotypes of familial
dilated cardiomyopathy. J Am Coll Cardiol 1998; 31:186–194.
marker of fibrosis, which also puts the patient at risk for
6 Mestroni L, Rocco C, Gregori D, et al. Familial dilated cardiomyopathy:
SCD. The use of electrophysiology studies has also been evidence for genetic and phenotypic heterogeneity. J Am Coll Cardiol
recommended as a screening tool. However, other data 1999; 34:181–190.
indicate that the need for or presence of a pacemaker 7 Jakobs PM, Hanson E, Crispell KA, et al. Novel lamin A/C mutations in two
families with dilated cardiomyopathy and conduction system disease. J Card
does not affect SCD risk [14]. A recent study [29

] did Fail 2001; 7:249–256.
not find that asymptomatic patients were at risk of SCD. 8 Hershberger RE, Hanson E, Jakobs PM, et al. Novel lamin A/C mutation in a
In the absence of conclusive data, there should be a family with dilated cardiomyopathy, prominent conduction system disease,
and need for permanent pacemaker implantation. Am Heart J 2002;
low threshold to place ICDs in these patients. It is clear 144:1081–1086.
that lamin A/C-deficient patients have a malignant 9 van Spaendonck-Zwarts KY, van den Berg MP, van Tintelen JP. DNA analysis
course and are at high risk for SCD. Knowledge of the
in inherited cardiomyopathies: current status and clinical relevance. Pacing
Clin Electrophysiol 2008; 31:S46–S49.
patient’s family history of SCD can help guide timing A review of the use of genetic testing in the evaluation, diagnosis, and treatment of
as well. patients with forms of inherited cardiomyopathy.
10 Rankin J, Auer-Grumbach M, Bagg W, et al. Extreme phenotypic diversity and

nonpenetrance in families with LMNA gene mutation R644C. Am J Med Genet
The fact that competitive sports may be a risk marker for 2008; 146A:1530–1542.
poor prognosis in patients with lamin A/C deficiency A series of patients with the same missense mutation. This study highlights the
variability in penetrance and phenotype for lamin A/C deficiency.
suggests that these patients may not fit into a standard 11 Hershberger RE. Familial dilated cardiomyopathy. Prog Ped Cardiol 2005;
cardiac paradigm [29

]. Earlier screening may be necess- 20:161–168.
ary if athleticism is detrimental in order to prevent 12 Crispell KA, Hanson EL, Coates K, et al. Periodic rescreening is indicated for
asymptomatic individuals from being too athletic. How- family members at risk of developing familial dilated cardiomyopathy. J Am Coll
Cardiol 2002; 39:1503–1507.
ever, data are limited and we would refrain at this time 13 Burkett EL, Hershberger RE. Clinical and genetic issues in familial dilated
from limiting activity based upon a potential risk rather cardiomyopathy. J Am Coll Cardiol 2005; 45:969–981.
than confirmed causality. 14 van Berlo JH, deVoogt WG, van der Kooi AJ, et al. Meta-analysis of clinical
characteristics of 299 carriers of LMNA gene mutations: do lamin A/C
mutations portend a high risk of sudden death? J Mol Med 2005; 83:79–83.
15 Meune C, van Berlo J, Anselme F, et al. Primary prevention of sudden death in
Conclusion patients with lamin A/C gene mutations. N Engl J Med 2006; 354:209–210.
FDC accounts for a larger proportion of IDC than has 16 Taylor MR, Fain PR, Sinagra G, et al. Natural history of dilated cardiomyopathy
been recognized by the clinical cardiology community. due to lamin A/C gene mutations. J Am Coll Cardiol 2003; 41:771–780.

There are multiple different genes that have been ident- 17 Sylvius N, Bilinska ZT, Veinot JP, et al. In vivo and in vitro examination of the
functional significances of novel lamin gene mutations in heart failure patients.
ified as causes of FDC in a limited number of patients, J Med Genet 2005; 42:639–647.
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myopathy with atrioventricular block: a lamin A/C defect-related disease. J Am
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system disease. N Engl J Med 1999; 341:1715–1724.
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20 Gruenbaum Y, Goldman RD, Meyuhas R, et al. The nuclear lamina and its
ventricular dysrhythmias. Clinicians should have high functions in the nucleus. Int Rev Cytol 2006; 226:1–62.
index of suspicion for the diagnosis of FDC and particu- 21 Shumaker DK, Kuczmarski ER, Goldman RD. The nucleoskeleton: lamins and
larly lamin A/C deficiency. Further, they should have a actin are major players in essential nuclear functions. Curr Opin Cell Biol
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22 Sylvius N, Hathaway A, Boudreau E, et al. Specific contribution of lamin A and
function and ventricular dysrhythmias.
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In-vitro study evaluating the effects of lamin A and C overexpression in COS7 cells.
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References and recommended reading differential effects on cellular function.
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referred to cardiogenetics outpatient clinics. Am Heart J 2007; 154:1130–
World Literature section in this issue (p. 260).
1139.
A series of patients with FDC who were screened for lamin A/C deficiency.
1 Karkkainen S, Peuhkurinen K. Genetics of dilated cardiomyopathy. Ann Med
This study found several different mutations that resulted in different clinical


2007; 39:91–107.
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dilated cardiomyopathy and apoptosis-triggered cardiac conduction system
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3 Michels VV, Driscoll DJ, Miller FA. Familial aggregation of idiopathic dilated presentation of lamin A/C deficiency. Lamin A/C-deficient myocytes demonstrated
cardiomyopathy. Am J Cardiol 1985; 55:1232–1233. apoptosis, particularly in conducting cells.
4 Baig MK, Goldman JH, Caforio AP, et al. Familial dilated cardiomyopathy: 26 Becane HM, Bonne G, Varnous S, et al. High incidence of sudden death with
cardiac abnormalities are common in asymptomatic relatives and may repre- conduction system and myocardial disease due to lamins A and C gene
sent early disease. J Am Coll Cardiol 1998; 31:195–201. mutation. Pacing Clin Electrophysiol 2000; 23:1661–1666.

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 208 Molecular genetics

27 van Tintelen JP, Tio RA, Kerstjens-Frederikse WS, et al. Severe myocardial 32 Rudenskaya GE, Polyakov AV, Tverskaya SM, et al. Laminopathies in Russian

fibrosis caused by a deletion of the 50 end of the lamin A/C gene. J Am Coll
families. Clin Genet 2008; 74:127–133.
Cardiol 2007; 49:2430–2439. A series of patients with lamin A/C deficiency who were genetically screened.
A family study demonstrating the malignant course that many patients with lamin Several novel mutations were discovered and mutational hot spots were identi-
A/C deficiency experience. The patients were at high risk for CHF and sudden death. fied.
28 de Backer J, van Beeumen K, Loeys B, Duytschaever M. Expanding the
33 Crispell K, Wray A, Ni H, et al. Clinical profiles of four large pedigrees with

phenotype of sudden cardiac death – an unusual presentation of a family with
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practice. J Am Coll Cardiol 1999; 34:837–847.
A family study that demonstrated that the risk of SCD preceded the development of
left ventricular dysfunction.
34 Michels VV, Moll PP, Miller FA, et al. The frequency of familial dilated
29 Pasotti M, Klersy C, Pilotto A, et al. Long-term outcome and risk stratification in cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy.


dilated cardiolaminopathies. J Am Coll Cardiol 2008; 52:1250–1260. N Engl J Med 1992; 326:77–82.
A large series of 164 patients in 27 families with lamin A/C deficiency. These
patients had a malignant course. The authors were able to identify several markers 35 Koikkalainen JR, Antila M, Lotjonen JMP, et al. Early familial dilated cardiomyo-
for risk of sudden death, including CHF, which is in contrast to previous studies.

pathy: identification with determination of disease state parameter from cine
Athleticism was also a risk factor for sudden death. MR image data. Radiology 2008; 249:88–96.
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30 Parks SB, Kushner JD, Nauman D, et al. Lamin A/C mutation analysis in a
A/C mutations who did not have clinical disease.


cohort of 324 unrelated patients with idiopathic or familial dilated cardiomyo-
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A large series of patients who were found to have lamin A/C deficiency. Multiple

nance imaging of myocardial contrast uptake and blood flow in patients
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affected with idiopathic or familial dilated cardiomyopathy. Am J Physiol Heart
family members were found to have the mutation, suggesting that not all lamin A/C
Circ Physiol 2008; 295:H1234–H1242.
defects cause disease.
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novel mutations were found and mutational hot spots were identified. Neuromuscul Disord 2008; 18:291–298.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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 "Be tranquil, my dear, it is not Isidore."
"Who then? I am dying to know."
"It is monsieur the millionaire of Nevada."
"That snake!"
"Gabrielle, you are dreadful. Do not talk like that. It is a fine
young man of an interesting type. His dress and manners are a little
unusual, perhaps, but he is tall and handsome, with an air of
melancholy quite engaging--like an artist or poet, I should say. And
he is rich. Yes, a distinguished-looking young man, a personage.
See, there he comes. Do not be rude to him, Gabrielle."
Gabrielle had no thought of being rude to Pamphile. On the
contrary, she did her best to amuse him while her mother was
preparing the dinner and her father was still in the hayfield. They
played croquet on the lawn, walked about in the garden, sat on the
green bench of the verandah looking out on the river and the
mountains, and all the while they talked of this and that, of the
scenery, the parish, the neighbours, the tourists, of Beauport,
Quebec and Montreal, of Chicago and the Far West, of Nevada and
the gold mines, of travel and adventure, of politics even, and
religion. Pamphile was nothing if not interesting, for he had travelled
much with his eyes open, was by nature of a ready wit and tongue,
and knew how to tell of what he had seen and had not seen with a
realistic abandon that was well-nigh irresistible.
At first Gabrielle could hardly conceal her aversion for Pamphile,
who was, she felt, some evil genius of the underworld; but presently
she forgot his outlandish dress, his gaudy jewellery, his long hair and
his unctuous suavity, and saw only the tall, handsome, mysterious
stranger who had descended upon the secluded valley from the
great, unknown world beyond the mountains. It was a pleasure to
hear him talk in an intimate way of people and things, to watch his
animated gestures and changing expression, to wonder what had
brought him to St. Placide and how long he would be able to stay.
Pamphile was a born story-teller, and, like most of his tribe, his
talk was chiefly of himself. He was the centre of every incident, the
hero of every adventure. He spoke of the river and the great lakes,
of mighty cities, of distinguished men, of the buffalo of the plains, of
Indians and bandits, of lofty mountains and precipitous cañons, of
cattle ranches and mining camps, of gamblers and shooting affrays;
and always it was Pamphile who had been wise and generous,
strong and brave, who had encountered all dangers, overcome all
difficulties, and who had arrived at last at the summit of his ambition
and was now enjoying a well-earned rest in the peaceful valley
before plunging once more into the tumult and struggle of the outer
world.
Gabrielle listened as one entranced, gazing in wonder at the
mobile yet inscrutable face of Pamphile. Here certainly was a new
type of man, such as she had not seen in St. Placide nor in Quebec,
and certainly not within the walls of the Ursulines. She tried to
imagine him in the garb of a priest, reading his breviary, hearing
confession, giving consolation. Absurd! And how would he look in
the uniform of the Garrison Artillery? Very funny, to be sure. He
would certainly need to have his hair cut. What a pity he had not
lived in the time of the Grand Monarch as an officer in a regiment of
cavaliers--the Carignan Regiment, for example? There he would have
been almost at home. But what a figure he would cut in the costume
of a habitant! Ridiculous! No, Pamphile was a citizen of another
world. In the West he was doubtless a great man, not at all out of
place, and it was not fair to judge him by the standards of St.
Placide. Why demand that he be exactly like other people? He was
different. Not bad, only different.
"Gabrielle," said Madame Taché, after Pamphile had gone away,
"you were right in your opinion of that man, after all. He is a species
of serpent, as you said."
"Why, Mama!" exclaimed Gabrielle, "He is a fine young man, of
an interesting type. His dress and manners are a little unusual,
perhaps, but he is tall and handsome, with an air----"
"Be silent, Gabrielle. I have changed my mind since I have been
able to observe him more closely. It is not his clothes, altogether, nor
even his hair, nor that drooping moustache, but a certain expression
of I know not what, an indefinable suggestion of evil. How glad I am
that he has gone!"
"But, Mama, you were quite polite to him, and Papa, too,
seemed to find him interesting."
"Naturally, one is polite to a guest. And he is interesting, far too
interesting. He is fascinating, almost, like a serpent. Your father, of
course, was glad to hear about the mines of Nevada. I hope he will
not send any money there. No, Gabrielle, that man is not to be
trusted, and I will not have him come again."
"But, Mama, he is to come to play a game of croquet to-morrow
afternoon."
"Gabrielle, did you invite him?"
"No, Mama. Yes. That is, he asked if he might come; and I,
what could I say?"
 "That is a pity, my daughter. You should have spoken to me.
What shall we do? We do not want to offend him. There, I have it.
You shall go down to Quebec in the morning, and we will send a
message of explanation to Monsieur Lareau. Mother Sainte Anne will
be glad to see you."
"Oh, Mama, not that!" cried Gabrielle, with tears in her eyes.
"Do not make me leave St. Placide just now, the lovely hills, the
green fields, the leafy trees, the cool air. This is not the time to go to
the city, so hot, so dusty. That little dark cell will be like a furnace, a
veritable purgatory. No, Mama, you do not mean it. Do not send me
away. It would be too cruel."
"Gabrielle, I am surprised at you. Usually you are glad to run
down to Quebec for a few days, and Mother Sainte Anne is always
kind. Nonsense, my dear child; you are too silly. You shall go, of
course, and in a few days, possibly, you may return. We shall see."
"Well," said Gabrielle, with a sigh of resignation, "I will go, if you
wish. You know best, Mama. As for that man from the West, he is
nothing to me. Do you think that I should run away with him? Oh, it
is to laugh. But he amuses me with his talk, I confess, like the
quack-doctor whom we saw at the fair in Quebec. Could you not let
me stay another day, one little day? One little afternoon's
amusement, one little game of croquet--what is that? We must not
offend people without reason, as you have said, even a man from
the wild and woolly West. Say yes, Mama."
"Yes, yes, Gabrielle, if you will only stop your chatter. You make
a person deaf. But remember--only one day, and you are not to see
that young man after to-morrow. Do not say when you will return.
That will remain undecided for the present."
 "Mama, you are lovely. You are a saint, an angel, a bird of
paradise. And I, too, am a species of bird, but very tame, I assure
you. Do not worry about me. I will not fly away, but only flutter
about for a few hours, and then hop meekly into the cage. It is a
nice cage, and Mother Sainte Anne is a dear soul. I have often
thought that I could be happy in that holy place for the rest of my
life. Those who leave the world, and give themselves, body and soul,
to the good God, find rest and peace on the bosom of infinite love,
and the devotion which they give is returned to them a thousand-
fold. Those are the words of Mother Sainte Anne herself. Oh, Mama,
do not cry. You are not going to lose me. I have my moments of
devotion, but they do not last long. I am too fond of you, of all my
dear friends, of this brave world, and the glories of the religious life
seem dim and far away. No, I have no vocation. There, dear, console
yourself. Good-night. Sleep well."
It is a pleasant game, croquet, not only because it affords
moderate exercise and demands a sufficient degree of skill, but also
because it permits of frequent pauses, when the players may
converse about the condition of the lawn, the position of balls and
wickets, the ethics of various plays, the state of the weather, and
what not, while they walk about on the soft grass, or rest, it may be,
on rustic benches in the shade of trees. It is a game for lovers in the
springtime of life, where there is no rivalry and where both may win.
But when a third party comes there is a sudden change, the spirit of
rivalry enters, and the innocent game becomes a form of war, a
phase of the age-long struggle of life and death.
"Ah!" exclaimed Gabrielle, as Pamphile made a long hit, "that
was a fine stroke. You play well, Monsieur Lareau, better than any
one in our parish; that is, better than all but one."
"But one, you say, Mademoiselle Taché?" said Pamphile,
affecting an air of indifference. "And who is that, if I may dare to
ask?"
"Oh," said Gabrielle, wishing to recall her words, "perhaps I am
mistaken, for it is a long time since I have seen him play, but I was
thinking of our neighbour, Monsieur Giroux."
"He?" said Pamphile, with a sneer. "The youth who was to have
been a priest? Yes, I remember him. He must be a man by this time.
Strange that he is still here among the stay-at-homes. Did he not
dare to venture out into the world, where he might meet with men?"
"Monsieur Lareau," said Gabrielle, seriously, "it is evident that
you do not know Monsieur Giroux, or you would not speak thus. He
is very brave and very determined, and it is for that reason that he
will not leave St. Placide."
"Oh, I can well understand, Mademoiselle," said Pamphile, with
a knowing smile. "While there are such attractions here it is no
wonder that he cannot tear himself away. For me, I also should like
to stay in St. Placide. Tell me to stay, Mademoiselle."
Gabrielle blushed furiously.
"Monsieur Lareau, you take liberties. As for Monsieur Giroux, I
know nothing of his affairs, but it is said that he has plans for the
improvement of the parish, for the exploitation of the forest, the
waterpower and all that."
"Plans?" drawled Pamphile. "Designs? Intentions? Well, I also
have plans, and I hope that the former candidate for holy orders will
not interfere with them. So he plays croquet, it seems. A noble
game, truly! I hope that he excels in other games demanding not
less of skill, but more of intellect, of courage."
"He does," replied Gabrielle, now enlisted in defence of the local
hero, "he knows how to play tennis, too, better than any of the
tourists; and draughts and chess, like a master. He throws the
hammer--oh, an enormous distance--and he can run like a deer, and
leap like--like--a grasshopper."
"A grasshopper? Name of an insect! Ha! Ha! That is good. What
a marvel, that priest that was to be! The sum of all the talents! But
permit me to ask, Mademoiselle the defender, if the excellent youth
knows how to shoot with the revolver, or with the rifle."
Gabrielle hesitated.
"Why do you ask, Monsieur Lareau?"
"Because," said Pamphile, between his teeth, "in the Far West
that is the first thing that one thinks of, and the last."
Gabrielle grew pale.
"Monsieur Lareau," she begged, "please forget what I have said.
I did not mean to offend you. Monsieur Giroux is nothing to me, but
when you speak contemptuously of one of the neighbours, I wish,
naturally, to defend him as much as possible. So please forgive me,
Monsieur. It was discourteous in me, I know."
"Say no more, Mademoiselle Taché; it is I who have offended. I
was perceiving a rival, that was all. If Jean Baptiste is not that he is
my dear old schoolfellow, of whom I have often thought during my
long years of exile. I should like to meet him again, for the sake of
old times."
"That could be arranged," said Gabrielle, with animation. "But
no, alas, I shall not be here, for I am going away to-morrow, to
Quebec."
Pamphile was aghast.
"To-morrow! And I had promised myself the pleasure of another
game of croquet. Not to-morrow, Mademoiselle--the day after to-
morrow, let us say."
"It is not I who decides these affairs, Monsieur, but my mother;
and she is inflexible."
"Ah, cruel parent! Yes, I see, I see. Because I am not an eligible
parti. Cruel parent! But surely Mademoiselle will return."
"Oh, yes, certainly. St. Placide is my home to which I return
frequently. Before the end of the summer, no doubt."
"The end of the summer! Alas, long before that time I shall be
on my way to Nevada, never to return. But will Mademoiselle be so
kind as to tell me where she will be staying at Quebec!"
"Certainly, Monsieur," said Gabrielle, pathetically. "At the
Convent of the Ursulines."
"A convent! Mon Dieu! Not to take the veil, I hope."
"Oh no," laughed Gabrielle, "not that, although I have
sometimes thought of it. No, only to stay a while to receive a little
more instruction in music, painting, embroidery, and all that. To
finish, to be finished, you know."
"Yes, I know," sighed Pamphile. "It is I who am finished. But
such is life. Mademoiselle Taché, you cannot imagine what a
pleasure it has been----"
"Yes, and for me also," said Gabrielle, with a sad little smile. "It
is such a pleasure to meet strangers, people who are different, you
know. No, I shall not forget you. But there is Mama calling me. I
must go. Good-bye, Monsieur Lareau. Good luck."
 "But Mademoiselle, I have something else to say."
"I cannot wait, Monsieur. Some one is coming."
"Mademoiselle, it is of great importance, a matter of life and
death, concerning our friend Monsieur Giroux, something which I
must tell to you, and you alone. Well, if you will not, it is all the
same to me. Adieu, Mademoiselle. Much pleased, I am sure."
"But, Monsieur Lareau, can you not write?"
"Absolutely impossible. To-morrow morning at sunrise I shall be
back there in the forest where the path crosses the little stream, and
I shall wait ten minutes."
"Monsieur, this is too much. I have the honour to bid you good
evening."
"Good evening, Mademoiselle, and many thanks for all your
kindness. And I shall be there at the time appointed."
On the following morning, as the sun rose above the hill,
peeping through the thick foliage he perceived Pamphile Lareau
reclining upon a mossy bank beside the little brook that flowed
through a shady glen to join the main river about half a league
below. His broad-brimmed hat lay on the ground beside him, his
long black mane fell on his neck and shoulders, and he was twisting
the ends of his moustache as he smiled expectantly--a smile that
was not good to see. In the clear morning light there was no illusion
of romance or chivalry about Pamphile. The glamour of the evening
twilight was gone, and he appeared as he was, a beast of prey, a
panther ready to spring upon the passer-by. Suddenly he became
aware of a presence, and glancing up he saw Gabrielle, pale and
beautiful as the morning, looking at him with awakened and startled
eyes. He saw no change in her, but smiled exultantly as he slowly
rose and held out his arms.
"A fine morning, Gabrielle."
Gabrielle drew back.
"You presume, Monsieur Lareau," she said, coldly. "You presume
upon a too slight acquaintance. But no matter. Will you have the
kindness to give me your message?"
"Oh, time enough for that. The day is young. Let us talk a little.
Let us look at the trees, listen to the birds, watch the clear stream as
it flows along. Let us enjoy the beauty of the morning, the charm
and seclusion of the woods. No? What?"
"I have no time for that," said Gabrielle, impatiently flicking her
boot with the riding-whip which she carried in her hand. "If you
please, Monsieur Lareau, give me the message."
"Message? There is no message," said Pamphile, with a leer.
"That was understood, was it not? It was only to say good-bye."
"No message?"
"No. That is to say, yes. A moment, Mademoiselle. Come back,
for the love of God. It is here, the message, the letter. Allow me to
hand it to you. It will explain everything. There, I have you, little
bird. Do not wriggle so. A kiss. One only. No? Then I take it--thus
and thus. Ah! Sacrée diable de femme! Sacré!"
Pamphile's note of triumph ended in a scream of rage and pain,
for Gabrielle, wrenching herself free from his grasp, turned on him
with flaming face and blazing eyes, and with the raw hide whip
struck him twice across the face. Immediately she fled up the path,
calling loudly for help.
"Jean! Jean! To me! To me! Ah, Mon Dieu! Jean! Jean!"
 With sublime faith in the hour of danger Gabrielle was
demanding a miracle; and lo! her cry was answered, for it was Jean
himself who came running down the path in time to catch her in his
arms as she was on the point of falling to the ground.
"Gabrielle, what is it? What is the matter, dear? Ah, I see. The
whip--give it to me. So it is you--thief, dog! Stand there! A fine face
you have. There, take that--and that! Shoot, would you? Drop it!
Good. Take two more! There! And there! It is a wonder I do not kill
you. Go!"
Pamphile slunk away like a whipped cur, but with murder in his
heart. Jean watched him until he disappeared in the forest, and then
turned slowly, as one in pain.
"Gabrielle!"
But Gabrielle was gone.
 CHAPTER XVI
THE TEMPTATION OF JEAN BAPTISTE

"Jean! Jean! To me! To me!"

The cry seemed but an echo in the recesses of the woods, yet
Jean could not rid himself of the feeling that Gabrielle was still in
danger and in need of help. The same vague sense of danger had
come to him a little while before, as he stood on the doorstep of his
house, smoking his pipe, watching the sunrise, and planning the
day's work, and had brought him running along the road to the
Taché place and thence down the woodland path to meet her whom
he loved best and him whom he most hated. They had met; the
danger was past; and now it seemed to Jean that he was totally
indifferent to Pamphile and that he hated Gabrielle more than any
other being in all the world. Answer her cry for help? Never again!
"Jean! Jean!"
The call was fainter now, with a note of reproach and the
suggestion of a sob, but Jean gave no heed. He only stood there, his
heart full of jealousy and anger, thinking evil thoughts. A strange
meeting, surely, on that lonely path at such an hour. A coincidence?
Hardly. Pre-arranged? Doubtless. To what end? Who can understand
the heart of a woman? To meet a stranger by accident on a Sunday
morning, after Mass, to have one visit and another, a game of
croquet, and then----. Love at first sight, it would seem, and after
that a rapid career, a swift descent into the depths. Inconceivable?
Yes. Impossible? Nothing is impossible. Even the holy angels could
fall from Heaven, and the Son of God might have bowed down to
Satan.
But the whip? Jean held it up in his clenched hand, a short but
heavy raw-hide with a knotted tail and loaded head, a dangerous
weapon in strong and determined hands. She had come alone, but
not unprotected. And those marks on the face of Pamphile? Inflicted
by the selfsame whip, evidently. By whose hand? The hand of
Gabrielle. Jean's heart gave a leap at the thought, and he almost
smiled. She had struck Pamphile twice with the knotted tail, and if
Jean had not come to the rescue she would have turned at bay and
felled her assailant to the ground with the leaden head. Brave
Gabrielle! A girl of spirit, that, a girl worthy of any man.
How then could she be ensnared by that spider, be fascinated
by that serpent? But she had broken the spider's net; she had
escaped the wiles of the serpent. A lover's quarrel? Only lovers
quarrel; the indifferent never. But do they strike each other with a
whip? No, thank God, Gabrielle did not love Pamphile. Impossible. As
for the rest, what matter? Strange, certainly, that meeting in the
woods, but not more strange than his own arrival in the nick of time.
The world itself is strange, and the combinations, the possibilities,
infinite. All is strange, mysterious, improbable. Nothing can be
explained. One must have faith in one's friends, in oneself, in God.
No; she cared nothing for that reptile. A passing fancy, perhaps, but
even that was over--else why the blow, the flight, the cry for help?
On whom does one call in the hour of danger? On one's friends, first
of all, and then, in the last extremity, on God.
"Jean! Jean!"
 A low voice seemed to call to him from the hill, a voice as of
one in tears.
Jean awoke from his reverie, and ran up the path.
"Gabrielle!" he called. "I am coming, dear. No danger. I am
here. Gabrielle! Gabrielle! where are you?"
The voice of Jean awoke the echoes of the hills, but there was
no other reply. On he ran with fear in his heart, peering into the
woods on either side, and calling incessantly, until he reached the
place where the path left the forest, and he could see the home of
Gabrielle nestling in a hollow in the midst of green fields, with its
white walls, its spacious verandah, its black roof with dormer
windows, and its massive stone chimney from which a wisp of yellow
smoke rose in the morning air. It was a picture of comfort and
security; and, as Jean looked upon the peaceful scene, he assured
himself that his fears were groundless and that all was well.
There was, however, a slight commotion about the place, such
as one might expect to see on a market day or on the departure of
some member of the family for a visit to the city. A large valise lay
on the verandah, and at intervals Madame Taché or a maid appeared
with a parcel or two, a parasol, a cloak, a basket. Monsieur Taché
and one of the men hurried to the barn; presently the great doors
were flung open and a prancing pair of bays came out with a
carriage, as though the family were going to Mass, to a wedding, or
some other notable celebration. Jean could hear the wheels crunch
on the gravel as they drove around to the front steps, where the
valise and the parcels were put on in front with the driver, while
Madame Taché and Gabrielle came out of the house all ready to
depart.
 It was Gabrielle herself, dressed all in white, like a bride, a white
cloak on her shoulders and a white hat with a single white plume
above her golden hair. Jean could not see her face in the distance,
but she seemed loth to go, for she ran hither and thither saying
good-bye to everybody, even to the chickens and geese, patted
Boule, the dog, on the head with a lingering caress, and then threw
her arms about her father's neck, sobbing bitterly.
Jean turned away with tears in his eyes, and when he looked
again the bays were prancing along the road, strong and proud, as
though carrying a queen and a princess to a wedding feast. Never
was princess more beautiful and more sad, for she had the air of
one who was forsaking all that she held most dear, and going away
never to return. As she passed near the place where Jean was
standing she looked up once with an appealing glance, but made no
sign of recognition or farewell. It was as if she did not see him, but
was looking beyond into the depths of the woods. As the carriage
came to the turn of the road Gabrielle turned and waved her
handkerchief toward her old home. Perhaps Jean was included in the
farewell. At any rate, he waved back, and as the carriage
disappeared from sight he thought he caught a flutter of white
meant for him alone.
Jean took a long breath, and then another, to keep down the
tide of emotion that was surging up from the depths of his soul.
Then, pulling himself together with a mighty effort, he sprang over
the fence and strode down the road toward his own home at a
terrific pace, as though to escape as fast as possible from the place
where he had seen the vanishing of all his hopes. For Jean did not
deceive himself; he understood it all; could see it all, as in a vision.
Gabrielle, that angel in the white robes, was leaving St. Placide--for
ever. She was going to a wedding--her own--in the chapel of the
Ursulines, before a congregation of black-robed sisters. She would
be a bride--the bride of Christ. They would cut off her golden hair,
dress her in black from head to foot, and make her say infinite
prayers by night and day on the cold, stone floor. Did Christ demand
that?
"I do not believe that He will have that," said Jean, aloud. "But
if so, I protest. It is not just. By Heaven, it is not! Ah, why did I not
answer at the first call? Why did I not follow? Fool that I was! Yes,
fool, fool!"
"Not so fast, Jean Baptiste," said a voice directly in front of him.
"Stop! You are running me down! Stop, I say! There you have done
it! Sacré diable! Fool! Yes, fool, fool!"
Jean stopped at last in his mad career, looked about in a dazed
manner, and saw a little old man picking himself up from the dusty
road, while filling the air with curses.
"Why, Monsieur Laroche, is it you? What is the matter? You fell
down? I ran over you? Surely not. Mon Dieu, Monsieur, if I did I am
sorry. Forgive me, I beg of you. It was an accident, I assure you. I
was not thinking; that is to say, I was thinking of something else.
There, Monsieur, allow me to brush off the dust, and to hand you
your hat. Oh, but I am sorry. What can I say?"
"Nothing!" said the old man, with a vicious snap of the jaws.
"Say nothing! Don't speak to me! I will get even with you. Yes, I will
punish you for this, Monsieur the Proprietor, Monseigneur the
Millionaire that is to be. Yes, I will show you."
 "Well, Monsieur Laroche, if you feel like that I can do no more.
Good-day, Monsieur."
"Not so fast, Jean Baptiste Giroux," said the old man, with
malicious deliberation. "Not so fast, my enterprising friend.
Remember, if you please, the little payment that is coming to me,
the half-yearly interest that will be due next week."
"Well, what of it?" said Jean.
"You will pay it," said the money-lender, with a leer, "on the very
day."
"Of course," said Jean, with contempt. "Is that all you wished to
say?"
"Yes. No," said the old man, taken by surprise, for he had
expected Jean to ask for an extension. "You will pay it when due--on
the very day? Well, I like that. It pleases me. It is not often that one
finds a young man of such a talent for affairs, of such promptitude.
It is a good sign, Jean Baptiste. You will succeed, no doubt, if you
have good luck. Yes, a promising young man. If only I had a partner
like you, a son-in-law. What? It could be arranged, could it not? The
little daughter has refused, of course, but might change her mind.
Who can tell? Women are variable, as you know. What do you say,
Jean, my lad--shall we have a try?"
"Monsieur Laroche," said Jean, earnestly, "I have the greatest
respect for Mademoiselle Blanchette, and I would not for the world
have you persuade her to change her mind. These marriages of
convenience are generally unsuitable and often terrible. It is a
dreadful thing--marriage without love."
Bonhomme Laroche laughed aloud.
 "Jean Baptiste Giroux, you talk like a fool. Marriage of
convenience? And why not? The union of two good farms, with
buildings, implements, cattle, horses, and all that, appears to me
very convenient and suitable. Moreover, on one side a fine hotel, on
the other an ample dowry--what better could you desire? Marriage
without love? It is to laugh. Go home, Jean; regard yourself in the
glass, and consider. Six feet in your stockings, straight as a
tamarack, broad shouldered, strong as an ox, a great chief, a leader
of men. What girl could not love a man like you? They have eyes,
those creatures, you may believe. And my Blanchette--what beauty,
what good temper, what capacity! Jean, my lad, it is all right; it will
go, it is a match made, I will say, in Heaven. Yes, say nothing; it is to
be."
Jean was speechless, for the little old man, pouring forth a
torrent of words, fairly danced with excitement and finally flung his
arms about the young man's neck in token of complete
reconciliation.
"Jean, Jean, my son. It will arrange itself. Say nothing. I will not
hear. Go. That little payment--forget about it. What is that among
friends; yes, relations. There, not a word. All is forgotten. Go home,
I say, for the present. Adieu! Adieu!"
It was still early in the morning, for Jean had been away from
home scarcely an hour--an hour that seemed an immeasurable time,
during which he had seen his past life unroll before him like a writing
in a foreign language, dark and meaningless. During that time he
had seen his ideals, his plans, his dream-castles melt away into
nothing, and all his future become a blank. The sun was still shining,
the clouds still floating in the sky, the grass still green, the birds still
singing, the air still fragrant with the odours of pine and balsam, of
crushed strawberries and new-mown hay--but not for him. The
world to him seemed colourless, odourless, silent as the tomb,
because the light and joy had gone out of his life when a young girl
with blue eyes and golden hair had passed down the road clad all in
white as a bride adorned for her husband. She had vanished at the
turn of the road, and immediately the world was changed.
The glory of the world had departed; the beauty was gone; love
had flown away; and life was no longer worth while. Even the great
house, the work of his hands, his castle and seat of pride, was like a
broken toy, a thing to be thrown aside. It had ceased to interest
him, but still the force of habit led him thither. He pressed the latch,
and entered the great kitchen where his good mother was preparing
breakfast.
"Good morning, Jean," she said, looking up with a smile, which
immediately changed to a look of alarm, "Oh, Jean, what is it? What
is the matter? Where have you been? What is it, Jean, my son?"
"It is nothing, my mother," he said, with a fugitive smile.
"Nothing at all. That is, I am a little tired, perhaps."
"Tired? A great man like you, and at this time of the day! Six
o'clock on a fine summer morning--and tired! Very strange, that. No,
Jean, you are putting me off. What is it, then? Tell me, my son."
"It is Bonhomme Laroche, my mother."
"That old miser. What does he want?"
"His money."
"His money? We have not had it six months, and the loan was
for three years."
 "It is the interest that he wants, my mother, the half-yearly
interest."
"Well, that is not much, a matter of sixty dollars or so. We will
pay him."
"Yes, we will pay him, of course, but we shall not have much
left."
"Nonsense, Jean! We shall have still a nice little deposit in the
bank; the tourists owe us a good sum; and to-morrow we shall send
butter and eggs to the market--five dollars worth at the very least.
No, there is no cause for worry. The business is going well. It will
come out all right, with the help of the good God. Have courage, my
son. The time of sowing will soon be over, and you will see the
golden harvest, the fruit of all your planning, your work. If that is all-
-no!"
"He wishes to buy a husband for his daughter."
"For his daughter--for Blanchette? Yes, I know. All the rest are
married--long ago. Only the little Blanchette is left. Not so very little
now, nor so very young. Let us see--ten, twenty, twenty-five, yes,
twenty-six years this summer. I remember well--fourteen years after
we came to the parish. They were sufficiently poor then, those
Laroches, poor and not at all proud. But they are not so very proud
even now, although quite rich. And the little Blanchette was pretty,
too, before the smallpox. A clever girl, and excellent housekeeper, a
manager from the bottom, a worker, too. No, it is not a bad
suggestion, not at all.
"Yes, she would be a fine partner for one who owns a hotel. No
fear of failure after that. All anxiety gone, all concern for the future.
The dowry would be considerable. She would have that fine farm,
with cattle, horses, pigs, sheep, implements, furniture, linen, and all
that, not to speak of money in the bank. Bonhomme Laroche has
explained it to me many times. A strange man, that. A miser, true,
but a just miser. He will have his money always, to the last sou, but
no more. I hope that we may be able to pay him all, when due.
There are great risks in an enterprise like this, and great
responsibilities. The alliance would settle everything, remove all
difficulties, dispel all clouds. Think of it, Jean. The two farms united--
a veritable estate, a seigniory, almost. Ah, my son, if your father
were alive, how pleased he would be!"
"My father," said Jean, thinking aloud, "would he have sold
himself in this way, I wonder?"
"Your father, Jean, would be pleased to see your prosperity, as I
have said, but for himself he did not regard such things. They had
no power over him. He did not know the value of money, that man.
For him truth, honour, a good name, were the true values, more
precious than rubies, more desirable than all the gold of the world.
And love? Yes, love above all. He also could have married an heiress,
the daughter of a rich merchant, a ship-owner. Beautiful she was, I
must confess, beautiful and accomplished. Yet he preferred me, me.
I never knew why. Ah, Mon Dieu, what devotion! Did he ever regret
it? He never said so. On the contrary, he assured me many times----
And I, did I regret the poverty, the work, the long years? No, it was
my glory. And you, Jean, my son, are like him, and I know what you
will do. Yes, and you are right, both of you. Land, cattle, money, are
very fine, all right in their place, but in comparison with love they do
not count for much. Ah, selfish old woman that I am to wish you to
give up so much for the sake of a dowry. Jean, my son, you shall
not, you could not."
"No, my mother, it would be impossible."
"Well, let us say no more about it. Let us think of something
else. There are still good fish in the sea, although they are often
hard to catch. That little Gabrielle, for example, the most beautiful
girl, they say, in all the parishes. Even in Quebec, there is not her
equal. They are rare, you know, blondes of that type, with hair like a
sunset cloud, not red, not gold, but something of both, and
changing with the light. And such a complexion, such a lovely face,
and a smile that touches the heart. A sufficiently good temper, also,
not meek, but high-spirited, polite and altogether charming. An
ample dowry, too, which is not to be despised when all the rest is
there. It contributes to independence and harmony.
"A most independent young lady, not easily caught, I should
say, but a prize for any fisherman. I have heard of several young
men who have aspirations--a brave young officer of the Artillery, for
one. They are dangerous rivals, those young soldiers, with their fine
clothes, their noble bearing, their self-confidence. I remember them
well. They are irresistible, almost. And Gabrielle is no ordinary
habitant girl, but one who would be at home in any society, high or
low. She will fly away some day, I fear. I don't like to think of that,
for the parish will be different without her. Yes, very different.
"But, Jean, what is the matter? Where are you going? Sit down
again, please. Your breakfast is just ready. See, I have something
that you like, a nice piece of ham, some eggs, and the most
delicious pancakes."
 "Thank you, dear," said Jean, wearily, "but I have no appetite
this morning."
"No appetite? That is serious. What is wrong? Work to do?
Nonsense! How can one work if one does not eat? Do not go, my
son. At least, come back soon, soon. There, I have driven him away.
Talkative old woman! Stupid old creature! My poor Jean!"

CHAPTER XVII
VENGEANCE

The brief summers are warm in St. Placide--how else could the crops
of hay, oats, and potatoes come to maturity?--but usually the nights
are cool, that the habitants, who have toiled many hours in the hot
sun, may enjoy refreshing sleep and be ready at the point of dawn
for the work of another day. But now and then, in the dog days,
there comes a blistering day, followed by a hot and sultry night,
when tired people lie awake for hours, longing in vain for rest.
The night following the departure of Gabrielle was such a night
as this, and Jean Baptiste, finding the heat of his attic insupportable,
went out on the railed terrace that crowned the roof, and lay down
under the stars. There was not a breath of air, and no sound to be
heard but the steady murmur of the river in the valley below. The
beasts that prowl by night made no noise; the bats flitted silently to
and fro; now and then an owl passed like a shadow; here and there
the lamp of a firefly glimmered and went out; and the stars twinkled
wearily as though they would fain close their eyes in sleep.
 Jean did not sleep, but lay thinking of his past life, his ambitions
and struggles, his hopes and fears, his successes and failures, as
though trying to strike a balance of profit and loss that should give
value to his life or show how empty it was of all worth and meaning.
He had always assumed that life was worth living--but why? In God's
name, why?
To know, to understand? He had read much in printed books
and in the book of nature; he had tried to think, to guess, to
imagine the answer to the riddle of existence, but with what result?
All was mystery, shrouded in darkness, silent, speechless, with only
a twinkling light here and there to lead--or mislead. To know? That
could not be the end of life, for what could one know? Nothing.
To love? Ah, there was something to fill the heart with joy--and
pain. When one finds a human being so beautiful that one would
gaze on her for ever, so sympathetic that in her company one has an
enduring sense of harmony and peace, so dear that one would fain
be with her until the end of time and afterwards in the eternal
world--when one finds such perfection of loveliness, surely it is the
perfection of existence to love and to be loved. Yes, but if one were
not loved. If in the early morning she went away, of her own free
will, to be the bride of another, what could one do with that
consuming love but tear it from the heart, that one might give
oneself heart and soul to the work of life?
The work of life? There at last was something for the strong
hand and brain, something to occupy the thought, to drive out the
spirit of despair, to fill the life with action, to cause one to forget the
mystery of existence and the shipwreck of love. To work, to build, to
create, to find the expression of oneself in the work of one's hands,
and, finally, like God, to pronounce it good--there was achievement
to satisfy the soul. If only the works of man, like the works of God,
could last for ever! Yet even these would pass away. Out of the
darkness of primeval chaos all had come; back to chaos and
darkness all would go. Yes, even the works of God. And God
Himself? What was He but the creator of a vain show, the spirit of
deceit and futility? It is written that He repented that He had made
Man. What wonder?
Jean Baptiste, as he lay there in the gloom of night, was
wandering, in thought, away from the realities of daily life, far from
the trodden paths, beyond all landmarks, into the confused and
misty regions where no reason dwells, but doubt, madness, and fell
despair, and where there is a downward path that plunges the lost
soul into the abyss.
From these evil dreams he was awakened by the rumbling of
thunder, and the falling of great drops of rain from a black cloud that
passed, like a curtain, across the sky. Flashes of lightning lit up the
valley, showing the trees of the forest bending before the wind,
while here and there a broken trunk stood erect with naked limbs
from which the branches had been torn by the fury of the gale.
Presently the storm arrived, shaking the house to its foundations;
the rain came down in torrents; and from the inky sky there fell lurid
forks of lightning followed by crashing thunder, the sound of falling
trees, and the cries of terrified beasts and men. It was a terrific, a
sublime spectacle, a display of power before which the timid soul
cowers and shrinks and seeks a place of refuge, a hole wherein to
creep, if by any chance it may escape the vengeance of the awful
power against which it cannot contend. Not so Jean Baptiste, who
enjoyed the refreshing bath of rain and the brilliant display of colour,
and to whom thunder claps were reassuring, since he knew that he
who hears the thunder has not yet been touched by the lightning.
But suddenly there appeared a great blaze of violet light, with a little
crackling noise, and for Jean Baptiste the show was ended. The bolt
of God had fallen upon La Folie, and the master of the house was
very close to death.
Immediately after this, as it seemed to Jean--it was more than
an hour--he felt himself roughly shaken, and heard a voice calling,
as from a great distance.
"Wake up! Wake up, Jean! Mon Dieu, will he never hear? Wake
up, I say. We must get down out of this."
"Get down?" said Jean, drowsily, without opening his eyes. "Get
down? But no, it is comfortable here. Let me alone, please. I am
sleepy, sleepy."
"There, you are all right, I see," said the voice, louder now. "But
get up, quick, quick! Get up, or I will throw you down. Sacré fou!
Take that!"
"Don't kick me," said Jean. Then, opening his eyes, he stared at
his assailant.
"Oh, it is you, Pamphile, and you kick me? Well, I don't wonder.
Do it again, my friend, and after that I will throw you off the roof.
But how black your face is! And where is your hair? Mon Dieu! What
has happened?"
"Happened? Sacré bleu! Your house is on fire. I tell you. Fire!
Fire! Get up, you cursed idiot, and save yourself. For the last time--
get up!"
 As Jean rose to his feet black volumes of smoke were rolling up
from the stairway, and he could hear the roar of flames below. He
started down the stairs.
"Not there, you fool!" yelled Pamphile. "I passed that way two
minutes ago, and see me now. This way! We can slip down the roof
on this side and then jump to the ground. Are you ready?"
"Yes," said Jean, slowly, "and I am sorry that I struck you with
the whip. It would have been better----"
"Shut up!" said Pamphile, savagely. "You shall pay for that, oh
yes. But at present we must save ourselves. Dieu, but it is hot! This
way. The roof will hold, I think. Prepare to jump in a moment. No,
that will not be necessary--they have placed a ladder. There is some
intelligence left, I see. Steady, now. Slowly. No danger. There, you
are on earth again. Par Dieu! It was a close shave. The roof has
fallen in. Madame, I have the honour to present to you Monseigneur
de la Folie, the biggest damn fool in St. Placide--yes, in all Canada."
"Listen to that," said one of the neighbours, who had hastened
to the scene at the first alarm. "That is what I have always said.
Jean Baptiste was a big fool to build a house like that--yes, a damn
fool, as Monsieur the millionaire has said. It is a brave man, that
millionaire. And Madame is glad to see her son again."
"Yes," said Bonhomme Gagnon, with an air of importance, "it
was I, you see, who was the first to arrive. Already the house was in
flames. The people were safe--that is to say, all but Jean, who sleeps
in the attic. Madame was distracted, frantic. 'Where is Jean? Oh,
where is Jean?' she screamed. 'Jean, my Jean! He will be burned to
death.' She rushed to the door, going to run upstairs through all the
smoke and flame. 'No, no, Madame,' I said, 'you cannot. Wait a
minute, Jean will waken, no doubt, in a moment. If not, I will go
myself.' But she would not listen.
"Then comes along Monsieur Pamphile, his face white as a
sheet, but all marked with red stripes as though some one had
struck him with a lash. What was the cause of that, I wonder? 'Stop,
Madame!' he cried. 'I will find the little priest. I will bring him down
to you.' He did not go in by the door--that was impossible--but
climbed up to one of the windows of the second floor, and went in.
'There is a good man gone to his death,' said I to myself. But
presently he appeared on the roof, as you have seen. It was lucky I
thought of the ladder, was it not? It was I who said: 'Bring the
ladder.' You heard me, Damase."
"Yes," said Damase Gosselin, with a smile; "you were saving the
life of a tourist, I think."
"Naturally," said Bonhomme Gagnon, with some asperity, "I was
assisting everybody."
"And meanwhile," continued Damase, "the millionaire from
Nevada ascends to the rescue of Jean Baptiste. It is a hero, that
millionaire. But where is he? Disappeared, vanished! That is the way
with heroes. They are modest people. One never hears them blow
their own horn."
"That is true," said Bonhomme Gagnon, nodding his head
vigorously. "The brave are always humble. That is the way with me,
for example. I never like to talk of myself, for fear somebody will
laugh at me. It is enough to have a good conscience, no matter
what people think. But I will tell you, in confidence, that it was I who
first saw the fire, who gave the alarm. Without me no Pamphile, no
Jean Baptiste descending by the ladder."
 The neighbours crowded about Bonhomme Gagnon, who went
on, impressively:--
"Yes, I heard the clap of thunder, of course. Who could sleep on
such a night? 'There,' I said, 'something was struck. La Folie,
perhaps, standing alone on the hill, with no lightning-rods.' I went to
look, but could see nothing. At the next flash there was La Folie, the
same as ever. It was only a tree, I thought. Soon the rain ceased,
and I sat on the steps smoking my pipe, and looking at the clouds as
they cleared away. I thought to myself: 'La Folie will get it sooner or
later. The good God does not love a man like Jean Baptiste, so
proud, so ambitious, so avaricious, one who would change
everything, overturn everything--an atheist, almost. Yes, the good
God will punish him some day.' It was prophetic, that thought of
mine, for after a while I saw a bright light in one of the windows at
La Folie, and then a great blaze that lit up the whole house. I made
a jump, you may be sure, called Marie, François, Isidore, Suzette--all
the family. 'Fire! Fire!' I called, and ran as fast as I could up the hill.
Dieu, but it was an excitement."
"What a pity that you cannot run fast, Monsieur Gagnon!" said
Damase. "If you had arrived sooner you might have saved Jean
yourself."
"Very true," said Bonhomme Gagnon, "and I would have done
it, you may be sure, but for those tourists. When I arrived they were
descending from the windows, some in night-gowns, some with
trousers on; and one, that Englishman over there, with all his
clothes, an eye-glass even. 'Here, my man,' he said, 'if you will bring
me a ladder I will step out of this, for it is deuced hot.' I was
carrying the ladder when Madame appeared wringing her hands,
and then came Pamphile, as you know."
"The Englishman offered to pay you well, no doubt," suggested
Damase.
"Yes. No. That is to say, he mentioned a certain sum, but I
could not think of it. I was saving life, you see, human life, which is
of more value than money. Afterwards, if he had felt that his life was
worth five or ten dollars, I might have been persuaded---- But I
could do nothing for him. Madame wanted the ladder for her son,
who, naturally, seemed of great importance to her, and I placed it by
the roof, just in time."
"Monsieur Gagnon," said Damase, emphatically, "you also are a
hero, that is evident. What a pity that such heroes cannot receive a
substantial reward--five dollars, at least, for every life that they save!
The life of that Englishman must be worth at least that amount. Let
us ask him for it, Monsieur Gagnon."
"No, no!" spluttered Bonhomme Gagnon. "I would not for the
world. He has lost his eye-glass, and is in a bad temper."
"True," said Damase, "and when you took the ladder away he
was in a fine rage. It was a pleasure to see him. His bath-tub also
was consumed, and his sponge. But the good God let him off easy
compared with poor Jean. But tell us, Monsieur Gagnon, is it true
Jean has said that the good God did not cause the fire? Is he really
an atheist, as they say?"
"Not so loud, Damase," whispered Bonhomme Gagnon. "He
might hear you. See him over there as he watches his fine house
burn to ashes. He is angry, as you may imagine. He has lost money--
more than the farm is worth. Insurance? None at all. He was a fool,
as Pamphile has said, one with too much confidence in himself and
too little in the good God. An atheist? Very likely. Who else would
want to build an hotel in St. Placide, to bring tourists to our peaceful
parish, to introduce strange fashions, to corrupt the youth, to
overturn everything? And he wishes to make a dam across the St.
Ange, to build a factory, to create a city. Yes, he would change all
the old ways, the good customs, the holy religion, even. An atheist?
Very likely. But the good God was against him, as we have seen, and
Jean Baptiste is finished. He will be a habitant, like the rest of us, or
he will leave the parish. Well, let him go. We were here before he
was born, and shall be all right after he is gone. St. Placide has no
need of Jean Baptiste."
The mind of Bonhomme Gagnon had been poisoned against
Jean by his association with Pamphile and Mère Tabeau, and the rest
of the neighbours were strangely ready to think ill of him and to
believe that he had been justly punished for his pride and
presumption. He had wished to set himself upon an eminence far
above the neighbours, and had tried to make himself a great lord, a
species of pope, in the parish of St. Placide; but the good God,
seeing that he held his head so high, had brought him down and
humbled him in the dust. His great house was a heap of ashes; his
plans were shattered, his prospects ruined; and he who had thought
himself the perfection of all the virtues, the sum of all the talents,
was finding by bitter experience that he was only a common man.
Every man must learn this lesson, sooner or later, that his pride may
be broken, his spirit chastened, that he may be able to bear the
yoke, to walk side by side with his fellows and to walk humbly before
his God. Thus the neighbours, by a strange mixture of piety and
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