MTM1基因突变致中央核肌病1例并文献复习  

Centronuclear myopathy caused by MTM1 gene mutation:a case report and literature review

作　　者：田雯 尹梦笛 秦怀雪 向龙[1] Tian Wen;Yin Mengdi;Qin Huaixue;Xiang Long(Department of Pediatrics,Chengdu First People′s Hospital,Sichuan610095,China)

机构地区：[1]四川省成都市第一人民医院儿科,610095

出　　处：《山西医药杂志》2023年第17期1310-1314,共5页Shanxi Medical Journal

摘　　要：目的总结1例儿童中央核肌病临床及基因突变特征并进行文献复习。方法回顾性分析2021年1至4月反复在成都市第一人民医院儿科门诊就诊及住院的1例诊断为中央核肌病患儿的临床资料。并抽取先证者外周血提取DNA进行高通量测序,发现了MTM1基因的1个错义突变。随后抽取患者父母的外周血对发现的突变进行验证,并进行突变致病性分析。结果患儿,男性,生后因“窒息复苏后33min”收入我科,查体上嘴唇呈倒“V”字形,下颌偏小,可见三凹征及漏斗胸,手指脚趾细长,肌张力低下,原始反射未引出。患儿因呼吸困难上机时间长,出院后家庭氧疗,因吞咽困难需管饲喂养,反复于我科门诊就诊及住院治疗,终因窒息抢救无效死亡。全外显子测序发现患儿MTM1基因存在错义突变c.142G>C(exon4)p.E48Q,结合患儿临床特点,确诊为X连锁隐性遗传中央核肌病(XLMTM)。家系验证变异遗传自母亲,母亲为健康表型。文献复习发现目前国内报道的MTM1突变致XLMTM病例较少,国外报道该类肌病表型非常严重,常在新生儿期发病并在婴儿期死亡。结论通过临床资料及基因分析确诊了1例自新生儿期发病的中央核肌病,基因分析证实了MTM1基因c.142G>C(p.E48Q)为该患儿的致病突变,该突变在国内外鲜有报道,拓展了MTM1基因的突变谱。结合文献复习旨在提高临床医师对该病的认识,早期明确诊断并为家属提供遗传咨询及产前诊断,避免同样疾病的再次发生。Objective To explore the clinical and gene mutation characteristics of a patient with centronuclear myopathy,and the relative knowledge was studied.Methods The clinical data of a child with centronuclear myopathy who repeatedly visited the pediatric outpatient and inpatient department of Chengdu First People's Hospital from January to April 2021 were retrospectively analyzed.Then DNA was extracted from the peripheral blood of the proband for high-throughput sequencing,neuromuscular disease-related genes were analyzed,and a missense mutation of MTM1 gene was found.Subsequently,the peripheral blood of the parents were sampled for sequencing,the sequencing results were compared with the normal sequence,and the pathogenicity of the mutation was analyzed.Results A boy was admitted to our department due to asphyxia after birth.Physical examination showed an inverted V-shaped upper lip,a small jaw,three concave signs and a funnel chest,slender fingers and toes,hypotonia,and no original reflex.The child was treated with oxygen therapy at home after discharge and tube feeding due to dysphagia.He was repeatedly treated in the outpatient department and hospitalized in our department,and finally died due to asphyxia.Whole exome sequencing revealed a missense mutation c.142G>C(exon4)p.E48Q in the MTM1 gene.Combined with the clinical characteristics of the child,he was diagnosed with X-linked recessive myotubular myopathy(XLMTM).The mutation was inherited from the mother,who had a healthy phenotype.Literature review found that few cases of XLMTM caused by MTM1 mutations have been reported in China,and foreign reports have shown that the phenotype of XLMTM is very serious,and the onset and death of XLMTM usually occur in the neonatal period.Conclusion This study confirms a pedigree with central nuclear myopathy by clinical examination and genetic analysis.The disease began in the neonatal period.Genetic analysis shows that MTM1 gene c.142G>C(p.E48Q)is the pathogenic mutation of this pedigree.This mutation is reported for the fi

关 键 词：肌张力过低 肌病 中央核 基因连锁 突变 

分 类 号：R725.9[医药卫生—儿科]