Key result
Among 37 Brazilian patients with ANO5-related myopathy, limb-girdle muscular dystrophy was the most common phenotype (67.5%), and the c.191dupA mutation was present in 56% of families.
Why the study?
ANO5-related myopathy is an important cause of limb-girdle muscular dystrophy and hyperCKemia, but main descriptions have emerged from European cohorts and its worldwide burden is unclear.
Cross-Sectional (n=37)
Yes
This large Brazilian cohort study demonstrates that the European founder mutation c.191dupA is highly prevalent in ANO5-related myopathy outside Europe, and that genotype does not determine phenotype.
Characterizes ANO5 myopathy in largest non-European cohort; extends European data but leaves open prospective validation.
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.
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Silva et al. (2019) conducted a cross-sectional in ANO5-related myopathy (n=37). Recessive variants in ANO5 was evaluated on Phenotypic presentation. Among 37 Brazilian patients with ANO5-related myopathy, limb-girdle muscular dystrophy was the most common phenotype (67.5%), and the c.191dupA mutation was present in 56% of families.
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