A Novel Locus for Dilated Cardiomyopathy, Diffuse Myocardial Fibrosis, and Sudden Death on Chromosome 10q25-26
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1 Journal of the American College of Cardiology Vol. 48, No. 1, by the American College of Cardiology Foundation ISSN /06/$32.00 Published by Elsevier Inc. doi: /j.jacc A Novel Locus for Dilated Cardiomyopathy, Diffuse Myocardial Fibrosis, and Sudden Death on Chromosome 10q25-26 Patrick T. Ellinor, MD, PHD,* Sabine Sasse-Klaassen, MD, Susanne Probst, MSC, Brenda Gerull, MD, Jordan T. Shin, MD, PHD,* Andrea Toeppel, PHD, Arnd Heuser, MD, Beate Michely, MD, Danita M. Yoerger, MD, Bong-Seok Song, MD, Bernhard Pilz, MD, Gregor Krings, MD, Bruce Coplin, MD,** Peter E. Lange, MD, G. William Dec, MD, Hans Christian Hennies, PHD, Ludwig Thierfelder, MD, Calum A. MacRae, MB, CHB, PHD* Charlestown and Boston, Massachusetts; Berlin and Cologne, Germany; and Albany, New York OBJECTIVES BACKGROUND METHODS RESULTS CONCLUSIONS We sought to identify the genetic locus for an inherited form of dilated cardiomyopathy (DCM) that is characterized by diffuse myocardial fibrosis and sudden death. Genetic studies have mapped multiple loci for DCM, which is a major cause of nonischemic heart failure; however, the genes responsible for the majority of cases have yet to be identified. Sixty-six family members were evaluated by 12-lead electrocardiogram (ECG), echocardiogram, and laboratory studies. Individuals with echocardiographically documented DCM were defined as affected. Subjects were considered unaffected if they were older than 20 years of age, had a normal ECG and echocardiogram, no personal history of heart failure, and had no affected offspring. Genotyping was performed using polymorphic markers. Genome-wide linkage analysis identified a novel locus for this inherited phenotype on chromosome 10q25.3-q Peak two-point logarithm of the odds scores 3.0 were obtained independently with each family using the markers D10S1773 and D10S1483, respectively. Haplotype analyses defined a critical interval of 14.0 centimorgans between D10S1237 and D10S1723, corresponding to a physical distance of 9.5 megabases. Multipoint linkage analyses confirmed this interval and generated a peak logarithm of the odds score of 8.2 indicating odds of 100,000,000:1 in favor of this interval as the location of the gene defect responsible for DCM in these families. We have mapped a novel locus for cardiomyopathy, diffuse myocardial fibrosis, and sudden death to chromosome 10q25-q26. The identification of the causative gene in this interval will be an important step in understanding the fundamental mechanisms of heart failure and sudden death. (J Am Coll Cardiol 2006;48:106 11) 2006 by the American College of Cardiology Foundation Heart failure is the leading cause of death in the developed world (1). Although atherosclerosis is the major underlying etiology, as much as one third of heart failure is a result of idiopathic dilated cardiomyopathy (DCM) (2), a condition with a substantial heritable component (3). In common with other inherited cardiac syndromes, DCM is characterized by genetic heterogeneity, and many of the responsible mutated genes have not yet been cloned (4 6). Molecular genetic studies have identified single-gene disorders in which DCM and apparently distinct clinical entities, such as hypertrophic cardiomyopathy (HCM), segregate as a single trait (7). Similar overlap between DCM and arrhythmogenic right ventricular cardiomyopathy has been demonstrated at other loci (8,9). A longitudinal study of the family members of From the *Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts; Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts; Max-Delbrueck Center for Molecular Medicine, Berlin, Germany; Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Franz-Volhard Clinic, HELIOS Clinics GmbH, Charité, Humboldt University Berlin, Berlin, Germany; Clinic for Pediatrics, Cardiology Division, Charité, Humboldt University Berlin, Berlin, Germany; **Albany Associates in Cardiology, Albany, New York; Department of Congenital Heart Disease, German Heart Institute Berlin, Berlin, Germany; and the Cologne Center for Genomics, Cologne, Germany. This project is supported by NIH awards to Dr. Ellinor (HL71632) and Drs. Ellinor and MacRae (HL75431) and by a Research Grant of the German Research Council (Ge 1222/1-2) to Dr. Gerull. Drs. Ellinor and Sasse- Klaassen contributed equally to this work. Manuscript received November 3, 2005; revised manuscript received December 30, 2005, accepted January 9, those with DCM has identified a broad range of phenotypes and substantial variation in the natural history of asymptomatic left ventricular dilation (10). Defining discrete subtypes of DCM using family studies will be critical for understanding the genetic basis of nonischemic heart failure. Where the genes for DCM have been identified, it is often a result of the pleiotropic nature of the associated syndromes. Thus, mutations in several sarcomeric protein genes, first identified in familial HCM, recently have been found in cases of DCM (11,12). Similarly, mutations in the genes encoding proteins from the dystrophin-associated glycoprotein complex and the lamin A/C gene have been implicated in DCM in the context of other phenotypic features, such as skeletal muscular dystrophy or conduction disease (13 15). Co-segregating sensorineural hearing loss was important for uncovering the role of EYA-4 mutations in one form of DCM (16). Work in distinctive forms of DCM has identified mutations in a number of other genes, including those encoding Z-disc proteins and, recently, mutations in the sodium channel SCN5A have been identified in a small number of kindreds with DCM, arrhythmias, and sudden death (17 20). The majority of DCM loci have been described only in single families exhibiting variable expressivity (4 6). We have identified two kindreds of European origin, CM-50 and CM-100, in which DCM with prominent diffuse interstitial myocardial fibrosis and sudden cardiac
2 JACC Vol. 48, No. 1, 2006 July 4, 2006: Ellinor et al. Locus for Dilated Cardiomyopathy and Sudden Death 107 Abbreviations and Acronyms CM cardiomyopathy DCM dilated cardiomyopathy HCM hypertrophic cardiomyopathy LOD logarithm of the odds death segregates as an autosomal-dominant Mendelian trait. METHODS Clinical studies were performed with institutional review board approval at Massachusetts General Hospital (Family CM-50) or the Charité, Humboldt University Berlin (Family CM-100). All family members had a physical examination and detailed interview to identify symptoms, past medical conditions, medications, and the medical history of all first-degree relatives. Each subject was evaluated by 12-lead electrocardiogram and echocardiogram both of which were interpreted using standard criteria (21). Coronary artery disease was excluded where indicated by selective coronary angiography (Table 1). Dilated cardiomyopathy was diagnosed on echocardiography if the left ventricular end diastolic dimension was 117% of normal when corrected for body surface area and there was evidence of impaired contractility, i.e., left ventricular ejection fraction was 0.50, or fractional shortening was 28% (21,22). Subjects were considered unaffected if they were older than 20 years of age, had a normal electrocardiogram and echocardiogram, no personal history of heart failure, and had no offspring with an abnormal electrocardiogram, echocardiogram, or a history of heart failure. The disease status of Table 1. Clinical Characteristics of Affected Family Members Number Age of Diagnosis/Age of Death ECG LVEF (%) LVFS (%) LVEDD (mm) LVEDD/ BSA (cm/m 2 ) Symptoms or Cause of Death Comments (Also See Text) CM-50 I-1 X/29 Unknown No autopsy performed II-2 X/54 Sudden death No autopsy performed II-7 X/45 AF Diffuse interstitial fibrosis II-12 X/41 Sudden death Aortic rupture post MVA III-2 44 NSR Asymptomatic III-4 X/36 Post OHT Interstitial fibrosis III NSR Minimal exertional symptoms III-13 X/27 NSR Post OHT Interstitial fibrosis and LVH, SCA III PAF Minimal exertional symptoms III-15 X/29 Sudden death Subendocardial fibroelastosis, LVH III-24 X/45 Normal exercise capacity; Interstitial fibrosis sudden death III-25 X/28 Sudden death Subendocardial fibroelastosis, LVH III-26 X/19 Acute respiratory distress No autopsy performed IV-2 19 NSR Asymptomatic IV-5 16 NSR Asymptomatic CM-100 I-1 X/43 CHF II-4 X/75 Pulmonary embolism Obligate carrier II-6 X/36 CHF II-7 X/38 CHF II-9 X/53 CHF III-5 20/28 CHF III-6 50/51 CHF III-10 38/48 CHF III-12 23/24 CHF IV-6 39 NSR CHF SCA IV-8 39 NSR CHF Obligate carrier IV-11 32/35 NSR CHF SCA IV NSR CHF SCA, atrial septal defect closure, interstitial fibrosis, obligate carrier V-3 17 NSR CHF V-4 8 NSR CHF, post-oht SCA, severe diffuse interstitial fibrosis V-5 20/25 NSR CHF SCA Deceased. AF atrial fibrillation; BSA body surface area; CHF congestive heart failure; LVEDD left ventricular end-diastolic dimension; LVEF left ventricular ejection fraction; LVFS left ventricular fractional shortening; LVH left ventricular hypertrophy; MVA mitral valve area; NSR normal sinus rhythm; OHT orthotopic heart transplantation; PAF paroxysmal atrial fibrillation; SCA selective coronary angiography; X not known.
3 108 Ellinor et al. JACC Vol. 48, No. 1, 2006 Locus for Dilated Cardiomyopathy and Sudden Death July 4, 2006: deceased individuals was based on medical records. All other family members were classified as of unknown affection status for the purpose of genetic analyses. Genome-wide linkage analysis was conducted using a 10- centimorgan resolution panel of polymorphic short tandem repeat markers (23). For fine mapping, additional markers in the region were typed, including a new CA repeat marker generated from sequence on chromosome 10 in deoxyribonucleic acid contig AC identified using the Ensembl Genome Browser. Primer sequences used for amplification of this marker were F: 5=-gtctctggaaattctctgaatgg-3= and R: 5=-tgttaagtctggtatagctacacc-3=. All genotypes were ascertained without knowledge of clinical status. Two-point and multipoint logarithm of the odds (LOD) scores were calculated assuming a disease penetrance of Allele frequencies were estimated from the general population, and the disease allele frequency was assumed to be Two-point LOD scores were calculated with the MLINK program (23). To estimate the most likely location for disease, multipoint LOD scores were calculated using the program SIMWALK2, with the markers D10S521, D10S1760, D10S597, D10S1773, D10S1237, D10S1693, AC027672, D10S1483, D10S1723, D10S1656, D10S217, and disease. The distances between loci and marker order were based on the Généthon genetic map (24). Candidate genes within the final interval were screened by direct sequencing of individual exons and flanking splice sites. Any nonsynonymous polymorphisms or splice-site sequence variants identified were then screened in a series of ethnically and racially matched control subjects. RESULTS In kindred CM-50 (Fig. 1A), 15 individuals were diagnosed with DCM, 4 were found to have an uncertain phenotype, and the remaining 17 family members studied were classified as unaffected (Table 1). Individual I-1 died at the age of 29 years, and 14 of his descendants suffered from idiopathic heart disease. Five individuals died suddenly with no symptomatic prodrome (II-2, II-12, III-15, III-24, and III-25). Two individuals developed significant heart failure and died after orthotopic heart transplantation (III-4 and III-13). In the remaining deceased individuals, there were minimal exertional symptoms until the terminal illness. None of the affected individuals had antecedent conduction system disease or skeletal muscle dysfunction. Disease onset occurred at a mean age of 34 years. A consistent feature of postmortem studies in deceased individuals from this family was gross and microscopic evidence of diffuse interstitial myocardial fibrosis, at times coalescing as subendocardial fibroelastosis. Surviving affected individuals demonstrate left ventricular dilation and depressed left ventricular function but relatively few symptoms of heart failure. In kindred CM-100 (Fig. 1B), 16 individuals were diagnosed with DCM, 6 were found to have an uncertain phenotype (II-1, III-2, IV-4, IV-13, V-2, and V-6), and the remaining 8 family members were classified as unaffected (Table 1). Individual I-1 died at age 43 years of congestive heart failure. Fifteen of his descendants had DCM. Nine affected individuals died prematurely from congestive heart failure. The index-patient (V-4) developed progressive heart failure requiring cardiac transplantation at 12 years of age. Histology of the explanted heart showed severe diffuse interstitial fibrosis without inflammation in the left ventricle (Fig. 2). Clinical data for other surviving affected individuals indicated early-onset disease between 17 (V-3) and 40 (IV-14) years of age (mean age of onset in kindred CM-100 was 32 years) with a rapidly progressive course. Two male individuals had minimal exertional symptoms and presented with significant ventricular chamber dilation at diagnosis, IV/11 at 32 years and V-5 at 20 years, and died within 3 and 5 years, respectively. None of the affected individuals had antecedent conduction system disease or skeletal muscle dysfunction. Three living individuals were assigned an uncertain status for various reasons: a prolonged episode of impaired ventricular function in the context of hyperthyroidism (IV-4); borderline left ventricular dimensions (V-2); or function (V-6). In most of the affected individuals in this family, echocardiography revealed a distinct pattern of segmental left ventricular hypokinesis involving the distal septum and apex. Independent peak two-point LOD scores of 3.39 ( 0.0) with marker D10S1773 for family CM-50, and 3.16 ( 0.0) with marker D10S1483 for family CM-100 were obtained. These LOD scores were highly robust to changes in penetrance (across a range from 0.95 to 0.60) or allele frequency (23). Haplotype analyses defined extensive overlap between the loci defined by each family, suggesting that these may be allelic. Definitive recombinant events in affected individuals from each family were identified using flanking markers from the two previously reported cardiomyopathy loci on Chromosome 10q (25,26). Analysis of microsatellite markers throughout the interval did not reveal a common haplotype between families CM-50 and CM Combining the haplotype data from both families defined a critical interval of 14.0 centimorgans between D10S1237 and D10S1723, corresponding to a physical distance of 9.5 megabases. A recombination event in affected individual IV-5 of family CM-50 defined D10S1723 as the distal flanking marker. The proximal flanking marker, D10S1237, was defined by a recombination event in affected individual IV-14 of family CM-100 (Fig. 1). Subsequent multipoint linkage analyses confirmed this interval and generated a peak LOD score of 8.2 at the marker AC (Fig. 3). 1-LOD unit down confidence intervals further supported this as the disease gene location (23). DISCUSSION Our data strongly support a novel locus on the distal long arm of chromosome 10 for DCM associated with distinctive clinical features, including diffuse interstitial myocardial fibrosis and sudden death. This is at least the third discrete
4 JACC Vol. 48, No. 1, 2006 July 4, 2006: Ellinor et al. Locus for Dilated Cardiomyopathy and Sudden Death 109 Figure 1. Pedigrees and haplotypes for families DCM-50 (A) and DCM-100 (B). Black symbols indicate individuals with cardiomyopathy; open symbols, unaffected status; and hatched symbols, unknown/indeterminate clinical status. The marker order from centromere to telomere is listed on the left of the figure, and the minimum disease haplotype for each family is enclosed in a box.
5 110 Ellinor et al. JACC Vol. 48, No. 1, 2006 Locus for Dilated Cardiomyopathy and Sudden Death July 4, 2006: Figure 2. Sirius red-stained histologic section from the left ventricle of individual V-4, family CM100. Connective tissue is evident as an intense red staining throughout the interstitium. locus for DCM on chromosome 10q and highlights the tremendous genetic heterogeneity underlying this disorder (Fig. 4) (20,25,26). Definitive insight into this heterogeneity will have to await the identification of the causative mutations at each locus, but the limited number of disease genes cloned to date suggest that DCM may be caused by perturbations of many proteins, including cytoskeletal or sarcomeric proteins, transcription factors, and ion channels (4,6,27,28). A prominent distinguishing feature of the disorder segregating at this novel locus is marked ventricular dilation with histological evidence of diffuse interstitial and subendocardial fibrosis or fibroelastosis (Fig. 2). This pattern of fibrosis is more commonly found in pediatric forms of DCM but has been reported in a distinct subset of adult explanted hearts (29). The age of onset of cardiomyopathy in the families we describe often is in the pediatric range, and these two kindreds may represent a forme fruste of the pathology observed in childhood cardiomyopathy. Myocardial fibrosis consistently is associated with sudden death in human cardiomyopathies, including DCM, HCM, Figure 3. Multipoint logarithm of the odds (LOD) score curve. The multipoint LOD score is plotted on the abscissa, whereas the recombination distance ( ) is plotted on the ordinate in centimorgans (cm) from an arbitrary origin set at marker D10S521. Figure 4. Ideogram of chromosome 10. The known loci and genes for dilated cardiomyopathy on chromosome 10 are illustrated. For a high-resolution map of this region, please also see the UCSC Human Genome Browser. and arrhythmogenic right ventricular cardiomyopathy. It has been hypothesized that this may result from the effects of fibrosis on myocardial electrical inhomogeneity or the association of fibrosis with abnormal intramyocardial coronary arterioles (30,31). Sudden death is a prominent feature of one of the families we describe (DCM-50) in which 5 affected individuals have died without prodromal symptoms at ages ranging from 19 to 54 years. Substantial fibrosis has been found in murine cardiomyopathy models caused by knockout of the genes encoding LIM domain proteins, such as cardiac LIM protein (CSRP3) and actinin-associated LIM protein (PDLIM3), or the cardiac restricted overexpression of a number of transgenes (32,33). It remains to be seen whether fibrosis and sudden death will be associated with discrete molecular pathways. The novel locus we have defined on chromosome 10 currently extends over approximately 14 cm or 9.5 Mb and includes at least 76 putative genes based on current public genomic databases (34). On the basis of the locations of the recombinant boundaries and the known structure of this region of the human genome, several positional candidate genes for DCM may be proposed. We have already screened by direct sequencing the most obvious candidates, including the genes encoding actin binding LIM protein 1 (ABLIM1), nebulin-related LIM protein (NRAP), and the phosphoinositide 5-phosphatase (INPP5F), each of which may have roles in the pathogenesis of cardiac fibrosis because their products contribute to the organization of the cytoskeleton, cell survival, or proliferation. Another plausible candidate for the cardiomyopathy described is the gene coding for BLC-2- associated athanogene 3 (BAG3), which interacts with heat shock protein 70 and regulates stress-induced apoptosis in the heart (35). Functional annotations of the remaining genes within the locus suggest that 13 of these codes for proteins are involved in signal
6 JACC Vol. 48, No. 1, 2006 July 4, 2006: Ellinor et al. Locus for Dilated Cardiomyopathy and Sudden Death 111 transduction, 10 for proteins fulfilling metabolic tasks, 3 for transcription factors, and 3 for structural proteins. The functions of proteins encoded by 39 novel genes are unknown. We are currently defining the cardiac expression of all transcripts in the minimal interval to prioritize genes for subsequent mutation screening. Because this is one of the few DCM loci for which independently mapped kindreds exist, it is also possible that we will identify additional families allowing us to refine the interval using new recombinants. Conclusions. We have defined a novel locus in two unrelated families for DCM with diffuse interstitial myocardial fibrosis and sudden death, suggesting that that it may be a distinct entity in the spectrum of human cardiomyopathies. The identification of the gene at this locus will be an important step in understanding the biologic basis of heart failure and sudden death. Acknowledgments The authors gratefully acknowledge the family members who participated in this study. The authors thank Prof. Dr. Peter Nurnberg, Prof. A. Rudolf Meyer, and Dr. David J. Milan for their help and advice. Reprint requests and correspondence to: Dr. Calum A. MacRae, Cardiovascular Research Center, th Street, 4th Floor, Charlestown, Massachusetts cmacrae@partners.org; or Dr. Ludwig Thierfelder, Max Delbrueck Center for Molecular Medicine, Robert Rossle Strasse 10, Berlin, Germany. lthier@mdc-berlin.de. REFERENCES 1. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002;347: Johnstone D, Limacher M, Rousseau M, et al. Clinical characteristics of patients in Studies Of Left Ventricular Dysfunction (SOLVD). Am J Cardiol 1992;70: Baig MK, Goldman JH, Caforio AL, Coonar AS, Keeling PJ, McKenna WJ. Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am Coll Cardiol 1998;31: Seidman JG, Seidman C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 2001;104: Chien KR. Genotype, phenotype: upstairs, downstairs in the family of cardiomyopathies. J Clin Invest 2003;111: Morita H, Seidman J, Seidman CE. Genetic causes of human heart failure. J Clin Invest 2005;115: Mogensen J, Klausen IC, Pedersen AK, et al. Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy. J Clin Invest 1999;103:R Olson TM, Keating MT. Mapping a cardiomyopathy locus to chromosome 3p22-p25. J Clin Invest 1996;97: Ahmad F, Li D, Karibe A, et al. Localization of a gene responsible for arrhythmogenic right ventricular dysplasia to chromosome 3p23. Circulation 1998;98: Mahon NG, Murphy RT, MacRae CA, Caforio AL, Elliott PM, McKenna WJ. Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease. Ann Intern Med 2005;143: Kamisago M, Sharma SD, DePalma SR, et al. Mutations in sarcomere protein genes as a cause of dilated cardiomyopathy. N Engl J Med 2000;343: Olson TM, Michels VV, Thibodeau SN, Tai YS, Keating MT. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science 1998;280: Towbin JA, Hejtmancik JF, Brink P, et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation 1993;87: Fatkin D, MacRae C, Sasaki T, et al. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med 1999;341: Lapidos KA, Kakkar R, McNally EM. The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ Res 2004;94: Schonberger J, Wang L, Shin JT, et al. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat Genet 2005;37: Towbin JA. Pediatric myocardial disease. Pediatr Clin North Am 1999;46: Olson TM, Michels VV, Ballew JD, et al. Sodium channel mutations and susceptibility to heart failure and atrial fibrillation. JAMA 2005; 293: McNair WP, Ku L, Taylor MR, et al. SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. Circulation 2004;110: Vatta M, Mohapatra B, Jimenez S, et al. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular noncompaction. J Am Coll Cardiol 2003;42: Mestroni L, Maisch B, McKenna WJ, et al. Guidelines for the study of familial dilated cardiomyopathies. Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy. Eur Heart J 1999;20: Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation 1980;62: Ott J. Analysis of Human Genetic Linkage. Baltimore, MD: The Johns Hopkins University Press, Dib C, Faure S, Fizames C, et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996;380: Mohiddin SA, Lu S, Cardoso JP, et al. Genomic organization, alternative splicing, and expression of human and mouse N-RAP, a nebulin-related LIM protein of striated muscle. Cell Motil Cytoskeleton 2003;55: Bowles KR, Gajarski R, Porter P, et al. Gene mapping of familial autosomal dominant dilated cardiomyopathy to chromosome 10q J Clin Invest 1996;98: Keating MT, Sanguinetti MC. Molecular and cellular mechanisms of cardiac arrhythmias. Cell 2001;104: Towbin JA, Bowles NE. Molecular genetics of left ventricular dysfunction. Curr Mol Med 2001;1: de Leeuw N, Ruiter D, Balk A, de Jonge N, Melchers W, Galama J. Histopathologic findings in explanted heart tissue from patients with end-stage idiopathic dilated cardiomyopathy. Transplant Int 2001;14: Lee AH, Gray PB, Gallagher PJ. Sudden death and regional left ventricular fibrosis with fibromuscular dysplasia of small intramyocardial coronary arteries. Heart 2000;83: Wheeler MT, Korcarz CE, Collins KA, et al. Secondary coronary artery vasospasm promotes cardiomyopathy progression. Am J Pathol 2004;164: Arber S, Hunter JJ, Ross J Jr., et al. MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure. Cell 1997;88: Pashmforoush M, Pomies P, Peterson KL, et al. Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy. Nat Med 2001;7: Kent WJ, Sugnet CW, Furey TS, et al. The human genome browser at UCSC. Genome Res 2002;12: Takayama S, Xie Z, Reed JC. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem 1999;274:
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