title: Absence of alpha-sarcoglycan and novel missense mutations in the alpha-sarcoglycan gene in a young British girl with muscular dystrophy.
abstract: An 11-year-old white female presented with progressive proximal muscle weakness and marked calf hypertrophy. Muscle biopsy showed severe dystrophy with normal expression of dystrophin. There was complete absence of the 50kDa dystrophin-associated glycoprotein (alpha-sarcoglycan). DNA analysis showed novel point mutations (one missense and one splicing) in the alpha-sarcoglycan gene at chromosomal location 17q21, confirming the diagnosis of limb-girdle muscular dystrophy type 2D (LGMD-2D). We believe this is one of the first confirmed white cases of primary alpha-sarcoglycanopathy identified in the UK. This case supports the assumption of a wide geographic prevalence of severe childhood onset autosomal recessive muscular dystrophy and genetic heterogeneity. In the future, with improved diagnostic accuracy it is likely that more cases demonstrating primary or secondary deficiency of alpha-sarcoglycan will be identified. We would recommend staining for dystrophin-associated glycoproteins (sarcoglycans) in all new cases of muscular dystrophy with normal dystrophin, and confirmation with DNA analysis where possible.
authors.affiliation: Muscle Clinic, Robert Jones and Agnes Hunt Hospital, Oswestry, Shropshire, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Quinlivan
authors.forename: S A
authors.initials: SA
authors.lastname: Robb
authors.forename: C
authors.initials: C
authors.lastname: Sewry
authors.forename: V
authors.initials: V
authors.lastname: Dubowitz
authors.forename: F
authors.initials: F
authors.lastname: Piccolo
authors.forename: J C
authors.initials: JC
authors.lastname: Kaplan
mesh_terms: D001706:Biopsy; D002648:Child; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002886:Chromosomes, Human, Pair 17; D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D006984:Hypertrophy; D007866:Leg / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D015995:Prevalence; D012326:RNA Splicing; D049031:Sarcoglycans
chemical_list: D018389:Codon, Nonsense; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D004247:DNA