Clinical and molecular findings in a cohort of ANO5-related myopathy

• Autor(a) principal: Dourado Junior, Mário Emílio Teixeira
• Data de Publicação: 2019
• Outros Autores: Silva, André M. S., Coimbra-Neto, Antônio R.; et al.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRN
• Texto Completo: https://repositorio.ufrn.br/handle/123456789/54227; https://doi.org/10.1002/acn3.50801
• topic: myopathy; cohort of ANO5-related; miopatia relacionada ao ANO5

Objective:ANO5-related myopathy is an important cause of limb-girdle muscu-lar dystrophy (LGMD) and hyperCKemia. The main descriptions have emergedfrom European cohorts, and the burden of the disease worldwide is unclear. Weprovide a detailed characterization of a large Brazilian cohort fANO5patients.Methods: A national cross-sectional study was conducted to describe clinical,histopathological, radiological, and molecular features of patients carrying reces-sive variants inANO5. Correlation of clinical and genetic characteristics with dif-ferent phenotypes was studied.Results: Thirty-seven patients from 34 nonrelatedfamilies with recessive mutations ofANO5were identified. The most commonphenotype was LGMD, observed in 25 (67.5%) patients, followed by pseu-dometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCK-emia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patientspresented axial involvement, including one patient with isolated axial weakness.The most affected muscles according to MRI were the semimembranosus and gas-trocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants inANO5were identified, and the c.191dupAwas present in 19 (56%) families. Sex, years of disease, and the presence of loss-of-function variants were not associated with specific phenotypes.Interpretation:We present the largest series of anoctaminopathy outside Europe. The most com-mon European founder mutation c.191dupA was very frequent in our population.Gender, disease duration, and genotype did not determine the phenotype.