G.P.222

Limb-girdle muscular dystrophy (LGMD) is defined as a muscular dystrophy with predominantly proximal distribution of muscle weakness. It includes a number of disorders with heterogeneous etiology. We determined the frequency of recessive LGMD subtypes (LGMD2A, LGMD2D, LGMD2I and LGMD2L) within a cohort of Czech LGMD2 patients using mutation analysis of the calpain3 (CAPN3), fukutin-related protein (FKRP), alpha-sarcoglycan (SGCA), and anoctamin5 (ANO5) genes. Last year we introduced next generation sequencing to accelerate patient diagnosis and to widen spectrum of analysed genes. We designed capture library to target the coding exons of genes responsible for all known types of LGMD and genes responsible for muscular dystrophy with similar phenotype to LGMD. We observed that mutations of the CAPN3 gene are the most common cause of LGMD2. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A, 4.1% for LGMD2I, 2.8% for LGMD2D, and 1.4% for LGMD2L. Using next-generation sequencing, we identified two patients with mutations in the gene encoding dysferlin (DYSF) – LGMD2B and a patient with mutations in the gene encoding beta-sarcoglycan (SGCB) – LGMD2E. In total, we determined mutations in 41% of Czech LGMD2 patients. This work was funded by the project of the Internal Grant Agency of the Czech Ministry of Health (NT/14574-3); the projects of the Czech Ministry of Education “CEITEC – Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068) and SuPReMMe (CZ.1.07/2.3.00/20.0045).