title: Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy.
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).
authors.affiliation: Day Neuromuscular Research Laboratory, Charlestown, Massachusetts 02129, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: I
authors.initials: I
authors.lastname: Illa
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.forename: C
authors.initials: C
authors.lastname: Serrano
authors.forename: J A
authors.initials: JA
authors.lastname: Urtizberea
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.forename: M B
authors.initials: MB
authors.lastname: Hamida
authors.forename: S
authors.initials: S
authors.lastname: Bohlega
authors.forename: E J
authors.initials: EJ
authors.lastname: Culper
authors.forename: A A
authors.initials: AA
authors.lastname: Amato
authors.forename: K
authors.initials: K
authors.lastname: Bossie
authors.forename: J
authors.initials: J
authors.lastname: Oeltjen
authors.forename: K
authors.initials: K
authors.lastname: Bejaoui
authors.forename: D
authors.initials: D
authors.lastname: McKenna-Yasek
authors.forename: B A
authors.initials: BA
authors.lastname: Hosler
authors.forename: E
authors.initials: E
authors.lastname: Schurr
authors.forename: K
authors.initials: K
authors.lastname: Arahata
authors.forename: P J
authors.initials: PJ
authors.lastname: de Jong
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015152:Blotting, Northern; D003001:Cloning, Molecular; D000073939:Dysferlin; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D005819:Genetic Markers; D008565:Membrane Proteins; D009124:Muscle Proteins