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

Abstract

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.

Clinical correlations and long‐term follow‐up in 100 patients with sarcoglycanopathies

“…Interestingly, 11% of patients presented with pseudometabolic symptoms, which had only rarely been reported previously [16]. Pseudometabolic phenotype is a rare but possible presentation of LGMD caused by mutations in sarcolemmal proteins, such as dystrophin ( DMD ), anoctamine 5, dysferlin, and proteins associated with α‐dystroglycan deficiency (fukutin‐related protein, guanosine diphosphate–mannose pyrophosphorylase B) [22–26]; therefore, mutations in these sarcolemmal proteins, including sarcoglycans, should be considered in undiagnosed patients with pseudometabolic symptoms.…”

Autosomal Dominant ANO5-Related Disorder Associated With Myopathy and Gnathodiaphyseal Dysplasia

“…7 The nonspecific myopathic findings in muscle biopsy and normal or mild myopathic motor units on EMG are consistent with previous reports. 5 To date, 9 missense ANO5 variants have been reported in heterozygous state, 1,8 3 of which, including p.Thr513Ile, are located in exon 15. Despite the fact that Thr513 is not evolutionarily conserved, several lines of evidence support pathogenicity of the ANO5 variant.…”

A Journey with LGMD: From Protein Abnormalities to Patient Impact

“…Anoctamin-5 is most abundant in skeletal muscles, where it helps regulate muscle contraction and relaxation. LGMD R12 (2L, anoctamin-5-related) is a very slow-progressing subtype with symptom onset well into adulthood (average age of 38 years; Table 5 ) [ 56 ]. Similar to LGMD R2, patients with LGMD R12 can present with classic limb-girdle (proximal) or Miyoshi myopathy (distal) symptoms.…”