Zhao Yan, Hu Jing, Zhao Zhe, Shen Hongrui, Bing Qi, Li Nan
Department of Neuromuscular Disease, Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang City, Hebei Province, 050051, PR China.
Muscle Nerve. 2016 Sep;54(3):432-8. doi: 10.1002/mus.25050. Epub 2016 May 25.
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.
兰尼碱受体1（RYR1）、肌球蛋白重链7（MYH7）和硒蛋白N1（SEPN1）突变与核心肌病相关。RYR1突变导致大多数中央轴空病（CCD）病例。
我们对8例临床病理诊断为CCD的中国患者进行了筛查。通过靶向二代测序（NGS）进行基因分析以鉴定致病基因。使用生物信息学方法评估变异的致病性，并通过桑格测序确认NGS结果。
在7例患者中鉴定出1个新的（p.L4578V）杂合错义突变。2例患者携带新突变，1例为p.M4640R，3例为p.R4861H，1例为p.R4861C。所有患者均有轻至中度严重程度的表型。组织病理学检查发现中央轴空和I型纤维为主。
NGS是鉴定CCD中RYR1变异的有效策略。然而，NGS揭示的基因结果必须与临床病理特征相结合以验证诊断。《肌肉与神经》，2016年 《肌肉与神经》54: 432 - 438，2016年。
