title: A novel locus for dilated cardiomyopathy, diffuse myocardial fibrosis, and sudden death on chromosome 10q25-26.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Sabine
authors.initials: S
authors.lastname: Sasse-Klaassen
authors.forename: Susanne
authors.initials: S
authors.lastname: Probst
authors.forename: Brenda
authors.initials: B
authors.lastname: Gerull
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Shin
authors.forename: Andrea
authors.initials: A
authors.lastname: Toeppel
authors.forename: Arnd
authors.initials: A
authors.lastname: Heuser
authors.forename: Beate
authors.initials: B
authors.lastname: Michely
authors.forename: Danita M
authors.initials: DM
authors.lastname: Yoerger
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Song
authors.forename: Bernhard
authors.initials: B
authors.lastname: Pilz
authors.forename: Gregor
authors.initials: G
authors.lastname: Krings
authors.forename: Bruce
authors.initials: B
authors.lastname: Coplin
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lange
authors.forename: G William
authors.initials: GW
authors.lastname: Dec
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Hennies
authors.forename: Ludwig
authors.initials: L
authors.lastname: Thierfelder
authors.forename: Calum A
authors.initials: CA
authors.lastname: MacRae
mesh_terms: D000293:Adolescent; D000328:Adult; D009202:Cardiomyopathies / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D016757:Death, Sudden, Cardiac; D005260:Female; D005355:Fibrosis; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype
chemical_list: D005819:Genetic Markers