title: Variable reduction of caveolin-3 in patients with LGMD2B/MM.
abstract: Mutations in the human dysferlin gene ( DYSF) cause autosomal recessive muscular dystrophies characterized by degeneration and weakness of proximal and/or distal muscles: limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Recently, an interaction between caveolin-3 and dysferlin in normal and dystrophic muscle (primary caveolin-3 deficiency; LGMD1C) was shown. In this study, clinical,morphological and genetic analysis was carried out in four independent LGMD2B/MM patients. All patients presented with an adult-onset, slowly progressive muscular dystrophy with variable involvement of proximal and distal muscles. We found complete lack of dysferlin in the four LGMD2B/MM patients. Secondary reduction of caveolin-3 was detected in three out of the four patients. Regular caveolae were detected along the basal lamina in two patients by electron microscopy. We provide further evidence that dysferlin and caveolin-3 interact in human skeletal muscle. It remains to be elucidated whether the loss of this interaction contributes to pathogenic events in muscular dystrophy.
authors.affiliation: Gene Center, Friedrich-Baur-Institute & Dept. of Neurology, Ludwig Maximilians University of Munich, Munich, Germany.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.forename: Christian
authors.initials: C
authors.lastname: Braun
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.forename: Maja
authors.initials: M
authors.lastname: Poppe
authors.forename: Christian
authors.initials: C
authors.lastname: Thirion
authors.forename: Carolin
authors.initials: C
authors.lastname: Schmidt
authors.forename: Herbert
authors.initials: H
authors.lastname: Schreiber
authors.forename: Ursula I
authors.initials: UI
authors.lastname: Knirsch
authors.forename: Dagmar
authors.initials: D
authors.lastname: Brummer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Müller-Felber
authors.forename: Dieter
authors.initials: D
authors.lastname: Pongratz
authors.forename: Josef
authors.initials: J
authors.lastname: Müller-Höcker
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
mesh_terms: D000328:Adult; D021941:Caveolae / Q000648:ultrastructure; D051244:Caveolin 3; D022461:Caveolins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000473:pathology / Q000503:physiopathology*; D009154:Mutation
chemical_list: C417736:CAV3 protein, human; D051244:Caveolin 3; D022461:Caveolins; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins