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.

中文翻译：

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Anoctamin 5 (ANO5) 肌营养不良症——三种不同的表型和一种新的组织学模式。

目的 Anoctamin 5 (ANO5) 是一种假定的细胞内钙激活氯离子通道。ANO5 的隐性突变可能从无症状的高CK 血症和运动诱发的肌痛到近端和/或远端肌肉无力出现。在这里，我们描述了三名 ANO5 相关性肌营养不良症无关患者的临床、病理和分子发现。方法 在这项回顾性研究中，我们分析了我们的数据库，其中包括 2004 年 10 月至 2019 年 2 月为诊断目的进行的 1700 份肌肉活检。患者由两名肌肉学专家参与，他们进行并分析了肌肉活检。肌肉活检在冷却的异戊烷中冷冻，低温恒温器切片，并常规染色和反应（最少 16 次染色）。一个自定义面板，包括 115 个基因（Nextera Rapid Capture，Illumina）和全外显子组测序分析，用于在没有明确病理诊断的情况下进行二代测序。结果 3 名患者被诊断为 ANO5 相关性肌营养不良症，所有患者均呈现共同的外显子 5 突变 c.191dup 加上复合杂合错义突变。他们表现出三种不同的表型（远端肌病、LGMD2L 和无症状性高CK 血症）。奇怪的是，所有三种肌肉活检均显示出不同的模式，但在其中一种中观察到大量参差不齐的红色纤维，几乎没有肌内膜炎症和部分 T 淋巴细胞浸润细胞。结论 ANO5相关性肌营养不良症是一种异质性疾病，具有不同的临床表型和不同的组织学模式，甚至可能类似于线粒体肌病。