Abstract：
Anoctaminopathies are a group of autosomal recessive skeletal muscle disorders with various clinical phenotypes, caused by anoctamin 5 (ANO5) gene mutations and the abnormal expression of ANO5 protein. Patients with recessive mutations in ANO5 present with variable symptoms ranging from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here, we describe the clinical, pathological, and molecular findings of two unrelated patients with ANO5-related muscular dystrophy (MD). Ninety-six histologically identified MD cases were subjected to next-generation sequencing using a customized panel of 54 genes (IIlumina Design Studio). Two patients were diagnosed with ANO5-related MD. One patient had a pathogenic homozygous mutation of c.1406G>A in exon 14, while the other patient had a novel heterozygous mutation of c.2141C>G in exon 19 of ANO5 gene. Both showed two different phenotypes (limb girdle MD and Miyoshi myopathy) and histomorphological patterns. Muscle biopsy of one patient in addition showed amyloid deposit in the walls of interstitial blood vessels. ANO5-related MD is a heterogeneous disease with different clinical phenotypes as well as genotypes. All muscle biopsies with unclassified muscular dystrophies should be subjected to Congo red stain. The results of this study suggest that screening for ANO5 gene should represent an early step in the diagnostic work-up of the patients with undiagnosed MD and persistent asymptomatic hyperCKemia, even when muscle biopsy histomorphology is normal.
摘要：
缺氧胺病是一组具有各种临床表型的常染色体隐性遗传骨骼肌疾病，5(ANO5)基因突变和ANO5蛋白的异常表达。在ANO5中隐性突变的患者表现出各种症状，从无症状的高CK血症和运动诱发的肌痛到近端和/或远端肌无力。这里,我们描述了临床，病态,以及两名与ANO5相关的肌营养不良（MD）无关的患者的分子研究结果。使用定制的54个基因组(IIluminaDesignStudio)对96个组织学鉴定的MD病例进行下一代测序。两名患者被诊断为与ANO5相关的MD。1例患者在第14号外显子有c.1406G>A的致病性纯合突变，而另一名患者在ANO5基因第19号外显子有c.2141C>G的新杂合突变。两者均显示出两种不同的表型（肢体带MD和Miyoshi肌病）和组织形态学模式。一名患者的肌肉活检显示，间质血管壁中存在淀粉样蛋白沉积。ANO5相关MD是一种具有不同临床表型和基因型的异质性疾病。所有具有未分类肌营养不良的肌肉活检应进行刚果红染色。这项研究的结果表明，筛查ANO5基因应该是诊断未确诊的MD和持续无症状的高CK血症患者的早期诊断工作。即使肌肉活检组织形态学正常。
