摘要目的:对 MYOT基因突变致肌原纤维肌病3型的临床表型特点、肌肉病理、基因突变及相关蛋白进行分析，并对该病进行文献复习和综述。 方法:回顾分析2018年12月于山东大学齐鲁医院确诊的1例 MYOT基因突变致肌原纤维肌病3型患者的临床表型特点、肌肉病理和基因检测结果。应用全外显子测序对患者进行高通量致病基因筛查，发现候选致病突变后应用Sanger测序技术对患者及家系成员进行突变位点的验证，同时对发现的 MYOT的基因突变位点进行功能学验证并结合相关文献进行复习综述。 结果:该患者为47岁女性，因双下肢无力8年就诊。肌电图检查示肌源性损害；肌肉病理提示部分肌纤维内异常物质沉积及镶边空泡。外显子组测序和Sanger测序发现患者携带 MYOT基因c.170C>T（p.Thr57Ile）杂合突变，其儿子、女儿也存在着相同的突变位点。患者儿子肌酸激酶水平升高，肌电图偶见自发电位，患者女儿无异常；患者2名弟弟未检测到上述变异位点。蛋白功能研究提示 MYOT基因c.170C>T突变可导致myotilin的部分空间结构发生改变，且p62蛋白与myotilin的异常聚集参与疾病的致病过程。经文献复习发现 MYOT基因c.170C>T（p.Thr57Ile）突变在外国人群中已有报道，但中国人群未见报道。 结论:MYOT基因突变所致的肌原纤维肌病3型的临床表现具有异质性，主要表现为下肢远端或近端肌肉无力。肌肉病理发现部分肌纤维内相关蛋白的异常沉积及镶边空泡。该病的精准诊断主要依赖基因检测，p62蛋白和myotilin蛋白的共定位现象为该病的诊断和分子机制研究提供了新的思路。

abstractsObjective:To analyze the clinical phenotypic characteristics, muscle pathology, genetic mutations and related proteins of myofibrillar myopathy 3 caused by mutation in MYOT gene, and to conduct a literature review and summary of this disease. Methods:A retrospective analysis of the clinical phenotypic characteristics, muscle pathology and genetic test results of a patient with myofibrillar myopathy 3 caused by mutation in MYOT gene diagnosed in Qilu Hospital of Shandong University in December 2018 was conducted. Whole exon sequencing was applied to conduct high-throughput screening of pathogenic genes in the patient. After finding candidate pathogenic mutation, Sanger sequencing was applied to verify the mutation sites in the patient and family members. Meanwhile, functional verification was carried out on the mutation sites found in MYOT gene, and the relevant literature was reviewed. Results:The patient was a 47-year-old woman with weakness in her lower limbs for 8 years. Electromyography showed myogenic changes. The muscle pathology suggested that there was deposition of abnormal substances and rimmed vacuoles within some muscle fibers. Gene testing showed that the patient was a carrier of the MYOT gene c.170C>T (p.Thr57Ile) heterozygous mutation, and her son and daughter also carried the same mutation at the same site. The son of the patient had an elevated creatine kinase level and spontaneous potential was occasionally observed on electromyography, while the daughter had no abnormalities. Two younger brothers did not carry the mutation. Protein functional studies suggested that the mutation of MYOT gene c.170C>T mutation can lead to the change of partial spatial structure of myotilin, and the abnormal aggregation of p62 protein and myotilin was involved in the pathogenesis of the disease. Literature review revealed that c.170C>T (p.Thr57Ile) mutation has only been reported in foreign populations. This is the first detailed report on the clinical phenotype, muscle pathology and gene function of MYOT-related myofibrillar myopathy type 3 in China. Conclusions:The clinical manifestations of myofibrillar myopathy type 3 caused by MYOT gene mutation are heterogeneous, mainly manifested as muscle weakness in the distal or proximal extremities. Muscle pathology reveals abnormal protein deposits and rimmed vacuoles within some muscle fibers. Accurate diagnosis of the disease depends on gene detection. The co-localization of p62 protein and myotilin protein provides a new idea for the diagnosis and molecular mechanism research of the disease.