LAUSR

Objective Anoctamin 5 ( ANO5 ) is a putative intracellular calcium-activated chloride channel. Recessive mutations in ANO5 may present from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here we describe the clinical, pathological, and molecular findings of three unrelated patients with ANO5 -related muscular dystrophy. Methods In this retrospective study, we analyzed our database which includes 1700 muscle biopsies performed for diagnostic purposes from October 2004 to February 2019. Patients were attended by two myology experts, who performed and analyzed the muscle biopsies. Muscle biopsies were frozen in cooled isopenthane, cryostat sectioned, and routinely stained and reacted (minimum 16 stainings). A custom panel, including 115 genes (Nextera Rapid Capture, Illumina) and whole-exome sequencing analysis, was used for next-generation sequencing in cases without a definite pathological diagnosis. Results Three patients were diagnosed with ANO5- related muscular dystrophy, with all presenting the common exon 5 mutation c.191dup plus a compound heterozygous missense mutation. They showed three different phenotypes (distal myopathy, LGMD2L, and asymptomatic hyperCKemia). Curiously, all three muscle biopsies showed different patterns, but numerous ragged-red fibers with little endomysial inflammation and partial invasion cell by T lymphocytes were observed in one. Conclusion ANO5- related muscular dystrophy is a heterogeneous disease with different clinical phenotypes as well as different histological patterns, which may even mimic a mitochondrial myopathy. The results of this study provide further knowledge of the clinical, histological, and pathological features related to ANO5 mutations.