A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26

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Item Type:	Article
Title:	A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26
Creators Name:	Ellinor, P.T., Sasse-Klaassen, S., Probst, S., Gerull, B., Shin, J.T., Toeppel, A., Heuser, A., Michely, B., Yoerger, D.M., Song, B.S., Pilz, B., Krings, G., Coplin, B., Lange, P.E., Dec, G.W., Hennies, H.C., Thierfelder, L. and MacRae, C.A.
Abstract:	OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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. RESULTS: Genome-wide linkage analysis identified a novel locus for this inherited phenotype on chromosome 10q25.3-q26.13. 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. CONCLUSIONS: 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.
Keywords:	Cardiomyopathies, Chromosome Mapping, Dilated Cardiomyopathy, Fibrosis, Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Human Chromosome Pair 10, Lod Score, Pedigree, Phenotype, Sudden Cardiac Death
Source:	Journal of the American College of Cardiology
ISSN:	0735-1097
Publisher:	Elsevier
Volume:	48
Number:	1
Page Range:	106-111
Date:	4 July 2006
Official Publication:	https://doi.org/10.1016/j.jacc.2006.01.079
PubMed:	View item in PubMed

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