On symptomatic heterozygous alpha-sarcoglycan gene mutation carriers.
Mutations in the human alpha-sarcoglycan gene on chromosome 17q21.2 have been shown to cause a severe childhood autosomal recessive muscular dystrophy, a less severe limb girdle muscular dystrophy, exercise intolerance, or asymptomatic hyperCKemia. Here, we describe the clinical findings in a German family harboring a 371 T > C (Ile124Thr) missense mutation in the alpha-sarcoglycan gene. Whereas our index patient, an 11-year-old girl homozygous for this mutation, presented with a severe Duchenne-like phenotype, 7 out of 12 heterozygous mutation carriers from three generations showed mild to moderate scapular winging. In analogy to symptomatic female dystrophinopathy carriers, our results suggest that heterozygous alpha-sarcoglycan gene mutation carriers can be symptomatic with selective muscle weakness. This finding may be attributed to an additional negative variation in a yet unknown modifier gene essential to the function of the sarcoglycan complex in shoulder girdle muscles.
Muskellabor, Department of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Dirk
D
Fischer
Stefania
S
Aurino
Vincenzo
V
Nigro
Rolf
R
Schröder
D015153:Blotting, Western; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D010375:Pedigree; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D049031:Sarcoglycans