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


  • P.T. Ellinor
  • S. Sasse-Klaassen
  • S. Probst
  • B. Gerull
  • J.T. Shin
  • A. Toeppel
  • A. Heuser
  • B. Michely
  • D.M. Yoerger
  • B.S. Song
  • B. Pilz
  • G. Krings
  • B. Coplin
  • P.E. Lange
  • G.W. Dec
  • H.C. Hennies
  • L. Thierfelder
  • C.A. MacRae


  • Journal of the American College of Cardiology


  • J Am Coll Cardiol 48 (1): 106-111


  • 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.