Open AccessClinical and molecular findings in a cohort of ANO5 ‐related myopathy
Author(s) -
Silva André M. S.,
Coimbra-Neto Antônio R.,
Souza Paulo Victor S.,
Winckler Pablo B.,
Gonçalves Marcus V. M.,
Cavalcanti Eduardo B. U.,
Carvalho Alzira A. D. S.,
Sobreira Cláudia F. D. R.,
Camelo Clara G.,
Mendonça Rodrigo D. H.,
Estephan Eduardo D. P.,
Reed Umbertina C.,
Machado-Costa Marcela C.,
Dourado-Junior Mario E. T.,
Pereira Vanessa C.,
Cruzeiro Marcelo M.,
Helito Paulo V. P.,
Aivazoglou Laís U.,
Camargo Leonardo V. D.,
Gomes Hudson H.,
Camargo Amaro J. S. D.,
Pinto Wladimir B. V. D. R.,
Badia Bruno M. L.,
Libardi Luiz H.,
Yanagiura Mario T.,
Oliveira Acary S. B.,
Nucci Anamarli,
Saute Jonas A. M.,
França-Junior Marcondes C.,
Zanoteli Edmar
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.50801
Subject(s) - medicine , myopathy , cohort , pathology
Objective ANO5 ‐related myopathy is an important cause of limb‐girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. Methods A national cross‐sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5 . Correlation of clinical and genetic characteristics with different phenotypes was studied. Results Thirty‐seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was 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 common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.