Ryanodine受体1(RYR1),肌球蛋白重链7(MYH7),硒蛋白N1(SEPN1)突变与核心肌病相关。RYR1突变导致大多数中枢核心疾病(CCD)病例。
我们筛选了8例临床病理诊断为CCD的中国患者。通过靶向下一代测序(NGS)进行遗传分析以鉴定致病基因。使用生物信息学方法评估变异体的致病性,和NGS结果通过Sanger测序证实。
一部小说(p.在7例患者中鉴定出L4578V)和RYR1中的杂合错义突变。两名患者携带了一种新的突变,1有p.M4640R,3有p.R4861H,1有p.R4861C.所有患者均有轻度至中度严重表型。组织病理学发现表明中心核和I型纤维占优势。
NGS是鉴定CCD中RYR1变体的有效策略。然而,NGS揭示的遗传结果必须与临床病理特征相结合以验证诊断。肌肉神经,2016肌肉神经54:432-438,2016。
Ryanodine receptor 1 (RYR1), myosin heavy chain 7 (MYH7), and selenoprotein N1 (SEPN1) mutations are associated with core myopathies. RYR1 mutations cause most cases of central core disease (CCD).
We screened 8 Chinese patients with clinicopathological diagnosis of CCD. Genetic analysis was carried out by targeted next generation sequencing (NGS) to identify causative genes. Variants were assessed for pathogenicity using bioinformatic approaches, and NGS results were confirmed by Sanger sequencing.
One novel (p.L4578V) and heterozygous missense mutations in RYR1 were identified in 7 patients. Two patients carried a novel mutation, 1 had p.M4640R, 3 had p.R4861H, and 1 had p.R4861C. All patients had mild to moderate severity phenotypes. Histopathological findings demonstrated central cores and type I fiber predominance.
NGS is an efficient strategy to identify variants in RYR1 in CCD. However, genetic results revealed by NGS must be combined with clinicopathologic features to validate the diagnosis. Muscle Nerve, 2016 Muscle Nerve 54: 432-438, 2016.