MTM1基因半合子突变及RYR1基因杂合突变致新生儿X-连锁肌管肌病2例临床分析

Clinical analysis of 2 cases of neonatal X-linked myotubular myopathy caused by MTM1 gene hemizygous mutation and RYR1 gene heterozygous mutation

目的 分析2例新生儿X-连锁肌管肌病(XLMTM)的临床表现及致病基因突变情况。方法 采集2例XLMTM患儿及其父母外周血,提取基因组DNA,进行全外显子组测序,经比对分析发现可疑变异位点,采用Sanger测序法进行验证。分析2例患儿的临床资料。结果 2例均为男性。例1出生时刺激无反应,无自主呼吸,出生1 min Apgar评分1分,出生5 min Apgar评分6分。例2出生时呼吸频率慢、表浅,刺激无反应,出生1 min Apgar评分5分,出生5 min Apgar评分7分。2例均四肢肌张力低下、肌力Ⅱ级,吞咽困难,隐睾。2例均给予呼吸机辅助、控制感染、鼻饲配方奶及其他对症支持治疗。基因检测结果显示,例1存在MTM1基因(c.584G>A p.Cys195Tyr)杂合突变,RYR1基因c.6251G>A(p.Arg2084Gln)和c.11516G>A(p.Ser3839Asn)杂合突变;例2存在MTM1基因c.1116delTp.Val373fs移码突变。结论 XLMTM患儿临床发病早,症状重,预后不良;MTM1基因有多个基因变异位点,例1为罕见的MTM1基因联合RYR1基因复合杂合突变,未见相关文献报道,例2为MTM1基因突变。早期进行基因检测对准确诊断XLMTM有重要意义。

Objective To analyze the clinical manifestations and pathogenic genes of 2 cases of neonatal X-linked myotubular myopathy(XLMTM).Methods The peripheral blood of 2 cases of neonatal XLMTM and their parents was collected,and the genomic DNA was extracted.Whole exome sequencing was performed.The suspicious variation sites were found by comparison and analysis,and were verified by Sanger sequencing.The clinical data of 2 cases were analyzed.Results Both two cases were male.Patient 1 had no stimulus response and no spontaneous breathing at birth.Apgar score was 1 at 1 min,and 6 at 5 min.Patient 2 had slow and shallow respiratory rate,and no stimulus response.Apgar score was 5 at 1 min and 7 at 5 min.Both two cases had hypodystonia,grade Ⅱ muscle strength,dysphagia and cryptorchidism,and received ventilator support therapy,infection control,nasal feeding formula and other symptomatic support therapy.Patient 1 was found missense mutation of MTM1 gene(c.584G>Ap.Cys195Tyr) and heterozygous mutation of c.6251G>A(p.Arg2084Gln) and c.11516G>A(p.Ser3839Asn) of RYR1 gene.Patient 2 was found c.1116delTp.Val373fs frameshift mutation of MTM1 gene.Conclusions XLMTM has the features of early clinical onset,severe symptoms and poor prognosis.There are multiple gene mutation sites of MTM1 gene.The compound heterozygous mutation of MTM1 and RYR1 genes in patient 1 is clinically rare and no relevant literature has been reported.Patient 2 is found MTM1 gene mutation.The early genetic detection of MTM1 mutation is of great significance for accurate diagnosis.