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...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。展开更多
目的:总结1例新生儿X连锁中央核肌病临床及遗传学特征并进行文献复习。方法:回顾性分析2024年4月临沂市妇幼保健院新生儿监护室收治的1例诊断为X连锁中央核肌病患儿的临床资料,并复习相关文献。结果:男性患儿,胎龄34+1周出生,有出生窒...目的:总结1例新生儿X连锁中央核肌病临床及遗传学特征并进行文献复习。方法:回顾性分析2024年4月临沂市妇幼保健院新生儿监护室收治的1例诊断为X连锁中央核肌病患儿的临床资料,并复习相关文献。结果:男性患儿,胎龄34+1周出生,有出生窒息史。头围大,隐睾,肌张力低,存在呼吸及吞咽功能障碍,最终家长放弃后死亡。全外显子测序发现MTM1基因存在无义突变c.70C>T:p.Arg24*,结合患儿临床特点,确诊为X连锁中央核肌病(X-linked myotubular myopathy, XLMTM)。家系验证变异为新发变异。复习文献及检索数据库发现目前国内报道的MTM1突变所致XLMTM病例较少,近5年来共18例,国外相对较多。MTM1-Leiden开放数据库截止到2024年4月29日,共发现568名变异个体的598个变异位点。国内外报道该类肌病多数表型较严重,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例新生儿期发病的X连锁中央核肌病,基因分析证实了MTM1基因c.70C>T:p.Arg24*为该患儿的致病突变,该突变为国内外首次报道,拓展了MTM1基因的突变谱。Objective: To summarize the clinical and genetic characteristics of a neonatal X-linked myotubular myopathy and review the literature. Methods: The clinical data of a case diagnosed with X-linked myotubular myopathy admitted to the neonatal care unit of Woman and Children’s Healthcare Hospital of Linyi in April 2024 were retrospectively analyzed, and the relevant literature was also reviewed. Results: The male infant was born with a gestational age of 34+1 weeks and had a history of birth asphyxia. He had a large head circumference, cryptorchidism, low muscle tone, respiratory and swallowing dysfunction, and eventually died after his parents gave up. Whole-exome sequencing found a nonsense mutation c.70C>T:p.Arg24* in the MTM1 gene. Based on the clinical characteristics of the child, the patient was diagnosed with X-linked myotubular myopathy (XLMTM). Family validation showed that the mutation was a new occurrence. Reviewing the literature and searching the database found that there are currently few cases of XLMTM caused by MTM1 mutations reported in China, with a total of 18 cases in the past five years, and relatively many cases abroad. As of April 29, 2024, the MTM1-Leiden open database has found a total of 598 mutation sites in 568 mutated individuals. It has been reported at home and abroad that most of the phenotypes of this type of myopathy are severe, often onset in the neonatal period and death in infancy. Conclusion: A case of neonatal-onset X-linked myotubular myopathy was diagnosed by clinical data and genetically confirmed, and the MTM1 gene c.70C>T:p.Arg24* was genetically confirmed to be the causative mutation in this child, which is the first report in China and abroad, and expands the spectrum of mutations in the MTM1 gene.展开更多
文摘目的 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。
文摘目的:总结1例新生儿X连锁中央核肌病临床及遗传学特征并进行文献复习。方法:回顾性分析2024年4月临沂市妇幼保健院新生儿监护室收治的1例诊断为X连锁中央核肌病患儿的临床资料,并复习相关文献。结果:男性患儿,胎龄34+1周出生,有出生窒息史。头围大,隐睾,肌张力低,存在呼吸及吞咽功能障碍,最终家长放弃后死亡。全外显子测序发现MTM1基因存在无义突变c.70C>T:p.Arg24*,结合患儿临床特点,确诊为X连锁中央核肌病(X-linked myotubular myopathy, XLMTM)。家系验证变异为新发变异。复习文献及检索数据库发现目前国内报道的MTM1突变所致XLMTM病例较少,近5年来共18例,国外相对较多。MTM1-Leiden开放数据库截止到2024年4月29日,共发现568名变异个体的598个变异位点。国内外报道该类肌病多数表型较严重,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例新生儿期发病的X连锁中央核肌病,基因分析证实了MTM1基因c.70C>T:p.Arg24*为该患儿的致病突变,该突变为国内外首次报道,拓展了MTM1基因的突变谱。Objective: To summarize the clinical and genetic characteristics of a neonatal X-linked myotubular myopathy and review the literature. Methods: The clinical data of a case diagnosed with X-linked myotubular myopathy admitted to the neonatal care unit of Woman and Children’s Healthcare Hospital of Linyi in April 2024 were retrospectively analyzed, and the relevant literature was also reviewed. Results: The male infant was born with a gestational age of 34+1 weeks and had a history of birth asphyxia. He had a large head circumference, cryptorchidism, low muscle tone, respiratory and swallowing dysfunction, and eventually died after his parents gave up. Whole-exome sequencing found a nonsense mutation c.70C>T:p.Arg24* in the MTM1 gene. Based on the clinical characteristics of the child, the patient was diagnosed with X-linked myotubular myopathy (XLMTM). Family validation showed that the mutation was a new occurrence. Reviewing the literature and searching the database found that there are currently few cases of XLMTM caused by MTM1 mutations reported in China, with a total of 18 cases in the past five years, and relatively many cases abroad. As of April 29, 2024, the MTM1-Leiden open database has found a total of 598 mutation sites in 568 mutated individuals. It has been reported at home and abroad that most of the phenotypes of this type of myopathy are severe, often onset in the neonatal period and death in infancy. Conclusion: A case of neonatal-onset X-linked myotubular myopathy was diagnosed by clinical data and genetically confirmed, and the MTM1 gene c.70C>T:p.Arg24* was genetically confirmed to be the causative mutation in this child, which is the first report in China and abroad, and expands the spectrum of mutations in the MTM1 gene.
