title: Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis.
abstract: We characterized the frequency of limb-girdle muscular dystrophy (LGMD) subtypes in a cohort of 76 Australian muscular dystrophy patients using protein and DNA sequence analysis. Calpainopathies (8%) and dysferlinopathies (5%) are the most common causes of LGMD in Australia. In contrast to European populations, cases of LGMD2I (due to mutations in FKRP) are rare in Australasia (3%). We have identified a cohort of patients in whom all common disease candidates have been excluded, providing a valuable resource for identification of new disease genes. Cytoplasmic localization of dysferlin correlates with fiber regeneration in a subset of muscular dystrophy patients. In addition, we have identified a group of patients with unidentified forms of LGMD and with markedly abnormal dysferlin localization that does not correlate with fiber regeneration. This pattern is mimicked in primary caveolinopathy, suggesting a subset of these patients may also possess mutations within proteins required for membrane targeting of dysferlin.
authors: Institute for Neuromuscular Research, The Children's Hospital at Westmead, Sydney, Australia.
authors: Harriet P
authors: HP
authors: Lo
authors: Sandra T
authors: ST
authors: Cooper
authors: Frances J
authors: FJ
authors: Evesson
authors: Jane T
authors: JT
authors: Seto
authors: Maria
authors: M
authors: Chiotis
authors: Valerie
authors: V
authors: Tay
authors: Alison G
authors: AG
authors: Compton
authors: Anita G
authors: AG
authors: Cairns
authors: Alistair
authors: A
authors: Corbett
authors: Daniel G
authors: DG
authors: MacArthur
authors: Nan
authors: N
authors: Yang
authors: Katrina
authors: K
authors: Reardon
authors: Kathryn N
authors: KN
authors: North
mesh_terms: D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D000073939:Dysferlin; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D049288:Muscular Dystrophies, Limb-Girdle / Q000145:classification / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D012189:Retrospective Studies; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology
chemical_list: D051242:Caveolin 1; C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins