ABSENCE OF ALPHA-SARCOGLYCAN AND NOVEL MISSENSE MUTATIONS IN THE ALPHA-SARCOGLYCAN GENE IN A YOUNG BRITISH GIRL WITH MUSCULAR-DYSTROPHY

An 11-year-old white female presented with progressive proximal muscle weakness and marked calf hypertrophy. Muscle biopsy showed severe dys trophy with normal expression of dystrophin. There was complete absenc e of the 50kDa dystrophin-associated glycoprotein (alpha-sarcoglycan). DNA analysis showed novel point mutations (one missense and one splic ing) in the alpha-sarcoglycan gene at chromosomal location 17q21, conf irming the diagnosis of limb-girdle muscular dystrophy type 2D (LGMD-2 D), We believe this is one of the first confirmed white cases of prima ry alpha-sarcoglycanopathy identified in the UK. This case supports th e 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 c ases demonstrating primary or secondary deficiency of alpha-sarcoglyca n will be identified, We would recommend staining for dystrophin-assoc iated glycoproteins (sarcoglycans) in all new cases of muscular dystro phy with normal dystrophin, and confirmation with DNA analysis where p ossible.