Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy

Nat Genet. 1998 Sep;20(1):31-6. doi: 10.1038/1682.

Abstract

Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

Publication types

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

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Blotting, Northern
  • Cloning, Molecular
  • Dysferlin
  • Female
  • Gene Expression
  • Genetic Markers
  • Humans
  • Male
  • Membrane Proteins*
  • Molecular Sequence Data
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophies / genetics*
  • Mutation*
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational

Substances

  • DYSF protein, human
  • Dysferlin
  • Genetic Markers
  • Membrane Proteins
  • Muscle Proteins

Associated data

  • GENBANK/AF075575