title: Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy.
abstract: OBJECTIVE
  Mutations in the skeletal muscle gene dysferlin cause two autosomal recessive forms of muscular dystrophy: Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). The purpose of this study was to define the genomic organization of the dysferlin gene and conduct mutational screening and a survey of clinical features in 21 patients with defined molecular defects in the dysferlin gene.
  
  
  METHODS
  Genomic organization of the gene was determined by comparing the dysferlin cDNA and genomic sequence in P1-derived artificial chromosomes (PACs) containing the gene. Mutational screening entailed conformational analysis and sequencing of genomic DNA and cDNA. Clinical records of patients with defined dysferlin gene defects were reviewed retrospectively.
  
  
  RESULTS
  The dysferlin gene encompasses 55 exons spanning over 150 kb of genomic DNA. Mutational screening revealed nine novel mutations associated with MM. The range of onset in this patient group was narrow with a mean of 19.0 +/- 3.9 years.
  
  
  CONCLUSIONS
  This study confirms that the dysferlin gene is mutated in MM and LGMD2B and extends understanding of the timing of onset of the disease. Knowledge of the genomic organization of the gene will facilitate mutation detection and investigations of the molecular biologic properties of the dysferlin gene.
authors.affiliation: Day Neuromuscular Research Laboratory, Massachusetts General Hospital East, Charlestown 02129, USA.
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authors.lastname: Liu
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authors.initials: I
authors.lastname: Richard
authors.forename: R
authors.initials: R
authors.lastname: Bashir
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authors.lastname: Britton
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authors.initials: SM
authors.lastname: Keers
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authors.lastname: Oeltjen
authors.forename: H E
authors.initials: HE
authors.lastname: Brown
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authors.initials: S
authors.lastname: Marchand
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authors.lastname: Bourg
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authors.lastname: Beley
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authors.lastname: McKenna-Yasek
authors.forename: K
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authors.lastname: Arahata
authors.forename: S
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authors.lastname: Bohlega
authors.forename: E
authors.initials: E
authors.lastname: Cupler
authors.forename: I
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authors.lastname: Illa
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authors.lastname: Majneh
authors.forename: R J
authors.initials: RJ
authors.lastname: Barohn
authors.forename: J A
authors.initials: JA
authors.lastname: Urtizberea
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: A
authors.initials: A
authors.lastname: Amato
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D000073939:Dysferlin; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins; D009124:Muscle Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins