A new mtDNA mutation in the tRNA(Leu(UUR)) gene associated with maternally inherited cardiomyopathy

Hum Mutat. 1994;3(1):37-43. doi: 10.1002/humu.1380030107.


We report a new mutation, a C to T transition at nt 3303 of mtDNA, in seven members of a family with cardiomyopathy and myopathy: the proband and two siblings had fatal infantile cardiomyopathy, whereas in three maternal relatives the disease manifested later in life as sudden cardiac death or as mitochondrial myopathy with cardiomyopathy. The mutation was homoplasmic in all tissues (including blood) from the proband and her brother, but heteroplasmic in blood from five oligosymptomatic or asymptomatic maternal relatives. This mutation disrupts a conserved base pair in the aminoacyl stem of the tRNA(Leu(UUR)). None of 70 controls carried the mutation. Our data indicate that this mutation is the genetic cause of the disorder in this family, and confirm that the tRNA(Leu(UUR)) is a "hot spot" for mutations in mtDNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Base Sequence
  • Cardiomyopathy, Dilated / genetics*
  • Child
  • Citrate (si)-Synthase / analysis
  • DNA Mutational Analysis
  • DNA, Mitochondrial / analysis
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mitochondrial Myopathies / genetics*
  • Molecular Sequence Data
  • Muscles / enzymology
  • Myocardium / enzymology
  • Nucleic Acid Conformation
  • Oxidoreductases / analysis
  • Pedigree
  • Point Mutation / genetics*
  • Polymorphism, Restriction Fragment Length
  • RNA, Transfer, Leu / chemistry
  • RNA, Transfer, Leu / genetics*


  • DNA, Mitochondrial
  • RNA, Transfer, Leu
  • Oxidoreductases
  • Citrate (si)-Synthase

Associated data

  • GENBANK/S72618