LGMD AUTOSOMAL RESSESSIVE AND DOMINANT: P.105Recessive limb-girdle muscular dystrophies in a Brazilian tertiary hospital: epidemiological, clinical and genetic profile

Abstract

The limb-girdle muscular dystrophys (LGMD) are a heterogeneous group of autosomal hereditary diseases that share common clinical and laboratory findings such as weakness and atrophy of proximal muscles, often affecting lower extremities first; elevated creatine kinase (CK) levels; and dystrophic findings on muscle biopsy. There is little information regarding the frequency of each LGMD-related mutation in Brazil. Describe the genetic and profile of recessive limb-girdle muscular dystrophies cases from a tertiary hospital from southeastern Brazil. The molecular data analyzes was accomplished by DNA extraction from peripheral blood, followed by analyzes from ANO5, FKRP, SGCD, GAA, CAPN3, SGCA, SGCG, DYSF, SGCB, TCAP genes through next generation sequencing (NGS panel). From 82 tested patients, 40 (49%) presented any mutation. From this, 29 in homozygosity or compound heterozygosity. Among patients with LGMD2 confirmed diagnosis, there was 11 LGMD2B, 8 with LGMD2A, 5 with LGMD2E, 2 with LGMD2I, 1 with LGMD2G and 2 with LGMD2L, this, not yet described in the Brazilian population. The gender distribution was: 13 male and 16 female. The patients mean age was 37,9 years, and the symptoms onset ranged from 1 to 58 years old, with a mean of 12,3. The mean age at diagnosis was 35.6 years. The mean CK value at diagnosis was 4327 U / L. The lung function test identified 16 patients with normal forced vital capacity, 3 with a mild restrictive pattern and 3 with a severe restrictive pattern. This data was not available in the medical record form 7 patients. The NGS panel was sensitive to detection of mutations related to the LGMD, being more frequent in the genes of dysferlin and calpain 3, similarly to reported in literature. LGMD2I, common in European populations, was less frequent in our cohort.