On symptomatic heterozygous alpha‐sarcoglycan gene mutation carriers

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Abstract
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.
Funding Information
  • Telethon (TIGEM-P10)
  • MIUR (PRIN 2001 and 2002)
  • d.lgs (502/92)