title: Patients with a non-dysferlin Miyoshi myopathy have a novel membrane repair defect.
abstract: Two autosomal recessive muscle diseases, limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), are caused by mutations in the dysferlin gene. These mutations result in poor ability to repair cell membrane damage, which is suggested to be the cause for this disease. However, many patients who share clinical features with MM-type muscular dystrophy do not carry mutations in dysferlin gene. To understand the basis of MM that is not due to mutations in dysferlin gene, we analyzed cells from patients in one such family. In these patients, we found no defects in several potential candidates - annexin A2, caveolin-3, myoferlin and the MMD2 locus on chromosome 10p. Similar to dysferlinopathy, these cells also exhibit membrane repair defects and the severity of the defect correlated with severity of their disease. However, unlike dysferlinopathy, none of the conventional membrane repair pathways are defective in these patient cells. These results add to the existing evidence that cell membrane repair defect may be responsible for MM-type muscular dystrophy and indicate that a previously unsuspected genetic lesion that affects cell membrane repair pathway is responsible for the disease in the non-dysferlin MM patients.
authors.affiliation: The Rockefeller University, Box 304, 1230 York Avenue, New York, NY 10021, USA. jaiswaj@rockefeller.edu
authors.forename: Jyoti K
authors.initials: JK
authors.lastname: Jaiswal
authors.forename: Gareth
authors.initials: G
authors.lastname: Marlow
authors.forename: Gillian
authors.initials: G
authors.lastname: Summerill
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mahjneh
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mueller
authors.forename: Maria
authors.initials: M
authors.lastname: Hill
authors.forename: Katsuya
authors.initials: K
authors.lastname: Miyake
authors.forename: Hannelore
authors.initials: H
authors.lastname: Haase
authors.forename: Louise V B
authors.initials: LV
authors.lastname: Anderson
authors.forename: Isabelle
authors.initials: I
authors.lastname: Richard
authors.forename: Sari
authors.initials: S
authors.lastname: Kiuru-Enari
authors.forename: Paul L
authors.initials: PL
authors.lastname: McNeil
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Simon
authors.forename: Rumaisa
authors.initials: R
authors.lastname: Bashir
mesh_terms: D000328:Adult; D017306:Annexin A2 / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D049310:Distal Myopathies / Q000235:genetics* / Q000378:metabolism*; D000073939:Dysferlin; D005089:Exocytosis; D005260:Female; D006239:Haplotypes; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000293:injuries / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D002118:Calcium