Dados do Trabalho

Título

Molecular investigation using NGS for Inherited Myopathies : experience of a Brazilian terciary center

Resumo

Background and Objectives: Inherited myopathies represent a large and variable group of disorders. The age of onset ranges from neonatal presentations to late-adult forms. Most of the conditions can be caused by multiple genes, making the unique gene testing unfeasible. Advances in next generation sequencing techniques and the participation of industry in providing no-cost panels has made this genetic evaluation a new reality in Brazil. Our aim is to present the experience of the use of these technologies in a terciary center and present the gene distribution among the main groups of inherited myopathies: congenital muscular dystrophy (CMD), congenital myopathy (CM), congenital myasthenia (CMS), mitochondrial myopathies (MiM), metabolic myopathies (MeM), myofibrilar and distal myopathies(M_DM), limb-girdle muscular dystrophy (LGMD). For analysis purposes we included distrophinopatly patients with the LGMD.
Results: We evaluated 427 patients and performed panel for 249 patients and whole exome sequencing for 178 patients presenting diagnostic rates of 69% for the exomes and 66% for the panels. We identified a genetic cause for the condition in 68% of patients with a hipotesis of canalopathy, 90% of the CMD, 76% of the MC, 72% of the CMS, 16% of the MiM, 58% of the MeM, 46% of the M_DM and 71% of the LGMD. Discussion: We showed the performance of NGS technologies among many highly curated patients for a particular phenotype. We had higher diagnostic rates for several groups of disorders such as CM, CMD, CMS and LGMD than previously reported in the literature. We linked this finding to a continuous vigilance among new genes in the literature and to the importance of the clinical phenotype stratification for the positive results. In the opposite direction, we had lower diagnostic rates for MiM than previously reported, but mtDNA variants were not yet checked. Conclusion: NGS has facilitated the diagnosis in the inherited myopathies but requires a careful assessment of its limitations. A detailed clinical assessment is very important to provide high diagnostic rates.

Palavras Chave

Inherited Myopathy, NGS, Exome

Área

Doenças Neuromusculares