A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is caused by mutations in the calpain 3 (CAPN3) gene. The clinical diagnoses of these cases in Bulgaria are very complicated, no protein analysis on muscular biopsy is available in our country, and genetic tests are the only possibility to clarify the diagnoses in clinically ambiguous cases. We screened 48 unrelated Bulgarian cases with preliminary diagnoses of different types of muscular dystrophy for mutations in the CAPN3 gene. Altogether, 20 families (42%) were found to carry mutations in the CAPN3 gene. Several misdiagnosed cases were clarified. Three novel and six recurrent mutations were identified. In total, 40% of the patients are homozygous for c.550delA, and 70% carry it at least on one allele. The affected group of women in our sample shows later onset, milder clinical manifestation, slower progression, and later invalidization.