title: Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s).
abstract: Limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), a distal muscular dystrophy, are both caused by mutations in the recently cloned gene dysferlin, gene symbol DYSF. Two large pedigrees have been described which have both types of patient in the same families. Moreover, in both pedigrees LGMD2B and MM patients are homozygous for haplotypes of the critical region. This suggested that the same mutation in the same gene would lead to both LGMD2B or MM in these families and that additional factors were needed to explain the development of the different clinical phenotypes. In the present paper we show that in one of these families Pro791 of dysferlin is changed to an Arg residue. Both the LGMD2B and MM patients in this kindred are homozygous for this mutation, as are four additional patients from two previously unpublished families. Haplotype analyses suggest a common origin of the mutation in all the patients. On western blots of muscle, LGMD2B and MM patients show a similar abundance in dysferlin staining of 15 and 11%, respectively. Normal tissue sections show that dysferlin localizes to the sarcolemma while tissue sections from MM and LGMD patients show minimal staining which is indistinguishable between the two types. These findings emphasize the role for the dysferlin gene as being responsible for both LGMD2B and MM, but that the distinction between these two clinical phenotypes requires the identification of additional factor(s), such as modifier gene(s).
authors: Department of Biochemistry and Molecular Biology, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba R3E 0W3, Canada.
authors: T
authors: T
authors: Weiler
authors: R
authors: R
authors: Bashir
authors: L V
authors: LV
authors: Anderson
authors: K
authors: K
authors: Davison
authors: J A
authors: JA
authors: Moss
authors: S
authors: S
authors: Britton
authors: E
authors: E
authors: Nylen
authors: S
authors: S
authors: Keers
authors: E
authors: E
authors: Vafiadaki
authors: C R
authors: CR
authors: Greenberg
authors: C R
authors: CR
authors: Bushby
authors: K
authors: K
authors: Wrogemann
mesh_terms: D001483:Base Sequence; D001706:Biopsy; D002170:Canada; D000073939:Dysferlin; D005260:Female; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins