SHORT COMMUNICATION A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients Albena Todorova & Bilyana Georgieva & Ivailo Tournev & Tihomir Todorov & Nadja Bogdanova & Vanyo Mitev & Clemens R. Mueller & Ivo Kremensky & Jürgen Horst Received: 27 December 2006 / Accepted: 2 February 2007 / Published online: 23 February 2007 # Springer-Verlag 2007 Abstract 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 homozy- gous 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. Keywords Limb-girdle muscular dystrophy . LGMD2A . Calpain 3 . CAPN3 Forty-eight unrelated Bulgarian cases with preliminary diagnoses of different types of muscular dystrophy, but with unknown disease causing mutation, were selected from our register and were screened for mutations in the calpain 3 (CAPN3) gene after written informed consent. All recorded patients with clinical diagnoses of limb-girdle muscular dystrophy (any type) were included in the study, as well as some Duchenne/Becker muscular dystrophy and spinal muscular atrophy patients with genetically unproved diagnoses. The boys with preliminary diagnoses of Duchenne/Becker muscular dystrophy were screened for deletions in the dystrophin gene, but no mutations were found; no positive family history of the disease was recorded. Both girls with spinal muscular atrophy type III were also genetically unconfirmed after screening for deletions in the SMNtel gene. No protein analysis on muscle biopsy was available in our country. Given the fact that protein diagnostics for limb-girdle muscular dystrophy type 2A (LGMD2A; OMIM 253600) is invasive (muscle biopsy) and neither totally specific nor totally sensitive, the only possibility to clarify the diagnoses in our patients is to proceed with genetic analysis. We report here 20 Bulgarian patients (two having affected sibs) with confirmed muta- tions in the CAPN3 gene and clarified clinical diagnosis for LGMD2A. Clinical data were collected from the patients’ medical records. The preliminary diagnosis was based only Neurogenetics (2007) 8:225–229 DOI 10.1007/s10048-007-0083-3 The first two authors contributed equally to this study. A. Todorova (*) : B. Georgieva : T. Todorov : I. Kremensky Laboratory of Molecular Pathology, University Hospital of Obstetrics and Gynecology, Sofia Medical University, 2 Zdrave Str., 1431 Sofia, Bulgaria e-mail: todorova_albena@abv.bg B. Georgieva : V. Mitev Department of Chemistry and Biochemistry, Sofia Medical University, Sofia, Bulgaria I. Tournev Clinic of Neurology, Alexandrovska Hospital, Sofia Medical University, Sofia, Bulgaria N. Bogdanova : J. Horst Institute of Human Genetics, University of Muenster, Muenster, Germany C. R. Mueller Department of Human Genetics, University of Wuerzburg, Wuerzburg, Germany