title: Familial dilated cardiomyopathy secondary to dystrophin splice site mutation.
abstract: BACKGROUND
  Idiopathic dilated cardiomyopathy (DCM) encompasses a heterogeneous group of disorders, posing significant diagnostic challenges. Genetic etiologies underlie an important subset of DCM, including 20 genes and 5 X-linked disorders to date. We report a family with a rare dystrophin gene alteration, identified after evaluation of asymptomatic children whose extended family history included cardiomyopathy, premature cardiac death, or cardiac transplantation.
  
  
  RESULTS
  Record review, clinical evaluations, and DNA samples were obtained from members of a 5-generation pedigree with early onset DCM. Five of 6 affected males experienced death or cardiac transplant in their second or third decades. No affected individuals had skeletal muscle weakness before acute cardiac decompensation. Dystrophin gene analysis of an affected family member revealed sequence alteration at the conserved 5' splice site of exon 1 of the muscle-specific isoform of dystrophin (IVS1 +1 G>T) and co-segregated with cardiac disease in this family.
  
  
  CONCLUSIONS
  Young males presenting with apparent isolated cardiomyopathy or acute myocarditis may harbor dystrophin mutations without overt skeletal muscle pathology. The etiology of familial risk was not evident in this pedigree before retrospective cardiovascular genetics assessment, highlighting ongoing diagnostic challenges and limitations of standardized screening panels (which do not include dystrophin) in patients with "idiopathic" DCM.
authors.affiliation: Department of Cardiology, Children's Hospital, Boston, MA 02115, USA. dita.obler.cgc@gmail.com
authors.forename: Dita
authors.initials: D
authors.lastname: Obler
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Wu
authors.forename: Va
authors.initials: V
authors.lastname: Lip
authors.forename: Elicia
authors.initials: E
authors.lastname: Estrella
authors.forename: Sally
authors.initials: S
authors.lastname: Keck
authors.forename: Coral
authors.initials: C
authors.lastname: Haggan
authors.forename: Marc
authors.initials: M
authors.lastname: Semigran
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Smoot
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002648:Child; D049029:Dystrophin-Associated Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011379:Prognosis; D012326:RNA Splicing / Q000235:genetics*; D018570:Risk Assessment; D015996:Survival Rate
chemical_list: D049029:Dystrophin-Associated Proteins