title: The mitochondrial DNA C3303T mutation can cause cardiomyopathy and/or skeletal myopathy.
abstract: OBJECTIVE
  Several mutations in mitochondrial DNA have been associated with infantile cardiomyopathy, including a C3303T mutation in the mitochondrial transfer RNA(Leu(UUR)) gene. Although this mutation satisfied generally accepted criteria for pathogenicity, its causative role remained to be confirmed in more families. Our objective was to establish the frequency of the C3303T mutation and to define its clinical presentation.
  
  
  METHODS
  Families with cardiomyopathy and maternal inheritance were studied by polymerase chain reaction/restriction fragment length polymorphism analysis looking for the C3303T mutation.
  
  
  RESULTS
  We found the C3303T mutation in 8 patients from 4 unrelated families. In one, the clinical presentation was infantile cardiomyopathy; in the second family, proximal limb and neck weakness dominated the clinical picture for the first 10 years of life, when cardiac dysfunction became apparent; in the third family, 2 individuals presented with isolated skeletal myopathy and 2 others with skeletal myopathy and cardiomyopathy; in the fourth family, one patient had fatal infantile cardiomyopathy and the other had a combination of skeletal myopathy and cardiomyopathy.
  
  
  CONCLUSIONS
  Our findings confirm the pathogenicity of the C3303T mutation and suggest that this mutation may not be rare. The C3303T mutation should be considered in the differential diagnosis of skeletal myopathies and cardiomyopathy, especially when onset is in infancy.
authors.affiliation: The H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Department of Neurology, Columbia Presbyterian Medical Center, New York, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Bruno
authors.forename: D M
authors.initials: DM
authors.lastname: Kirby
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: B
authors.initials: B
authors.lastname: Garavaglia
authors.forename: G
authors.initials: G
authors.lastname: Duran
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: L K
authors.initials: LK
authors.lastname: Shield
authors.forename: W
authors.initials: W
authors.lastname: Xia
authors.forename: S
authors.initials: S
authors.lastname: Shanske
authors.forename: J D
authors.initials: JD
authors.lastname: Goldstein
authors.forename: R
authors.initials: R
authors.lastname: Iwanaga
authors.forename: Y
authors.initials: Y
authors.lastname: Akita
authors.forename: F
authors.initials: F
authors.lastname: Carrara
authors.forename: A
authors.initials: A
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: Zeviani
authors.forename: D R
authors.initials: DR
authors.lastname: Thorburn
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002648:Child; D004272:DNA, Mitochondrial / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial