KLHL40基因变异致双胎同患杆状体肌病8型并文献复习  

Nemaline myopathy type 8 caused by KLHL40 gene in a twin:case report and literature review

作　　者：赵珣 蔡姣 吴莎 马丽 胡扬 吴倩 熊伟 王榜珍 杨萌婷 许键炜 冯占辉 陈晓霞 陈茂琼 Zhao Xun;Cai Jiao;Wu Sha;Ma Li;Hu Yang;Wu Qian;Xiong Wei;Wang Bangzhen;Yang Mengting;Xu Jianwei;Feng Zhanhui;Chen Xiaoxia;Chen Maoqiong(Department of Neonatology,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;National Joint Local Engineering Laboratory for Cell Engineering and Biomedicine Technique(Guizhou Province Key Laboratory of Regenerative Medicine,Key Laboratory of Adult Stem Cell Translational Research,Chinese Academy of Medical Sciences),Guiyang 550000,China;Department of Scientific Research,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学附属医院新生儿科,贵阳550004 [2]细胞工程生物医药技术国家地方联合工程实验室,贵州省再生医学重点实验室,成体干细胞转化研究重点实验室(中国医学科学院),贵阳550000 [3]贵州医科大学附属医院科研处,贵阳550004

出　　处：《中华围产医学杂志》2023年第12期1007-1014,共8页Chinese Journal of Perinatal Medicine

基　　金：2021年贵州医科大学附属医院院级临床研究(2021-GMHCT-001);贵州省基础研究计划(自然科学项目)(黔科合基础-ZK[2022]一般415)。

摘　　要：目的探讨KLHL40基因变异致杆状体肌病8型(nemaline myopathy type 8,NEM8)的临床、遗传学和病理学特点。方法回顾性分析2022年7月贵州医科大学附属医院收治的双胎NEM8患儿的临床资料、家系基因测序及骨骼肌病理学资料。以“杆状体肌病8型”“线状体肌病8型”和“KLHL40”为关键词检索中国知网、维普中文期刊数据库、万方数据库和中华医学期刊全文数据库,并以“nemaline myopathy 8”和“KLHL40”为关键词检索PubMed、Embase和Web of Science数据库。检索时间为2007年1月至2023年2月。连同本单位收治的病例,分析所获病例的临床、遗传学及骨骼肌病理特点。对数据资料采用描述性统计分析。结果(1)病例资料:本单位收治的患儿(Ⅳ-2和Ⅳ-3)系异卵双胎,第2胎第2产。患儿母亲为体外受精-胚胎移植术受孕,分娩胎龄37周+1。患儿外祖母有唇、腭裂。第1胎(Ⅳ-1)左侧耳廓缺如,双手指末节挛缩,双足“马蹄”内翻足,因呼吸衰竭,于生后2 h死亡。2例胎儿期存在水肿,胎动延迟,其中一胎右足内翻;均有产时窒息;临床表现均为全身肌无力、呼吸衰竭、吞咽困难、多发关节挛缩及骨折。患儿生后以呼吸机维持生命53 d,家属放弃治疗,患儿死亡。全外显子组测序发现2例患儿为KLHL40基因c.1779G>T(p.W593C)纯合变异,其父母亲为KLHL40基因c.1779G>T(p.W593C)杂合变异,均为未报道位点。骨骼肌病理提示肌纤维纤细而圆,呈胎儿型,未见杆状体。(2)文献复习:检索到文献15篇、病例27例,连同本单位的2例,共29例NEM8病例,其中21例活产,8例引产;7例(24.1%)有阳性家族史;19例(65.5%)胎儿期存在异常,包括胎动障碍、羊水增多、关节挛缩及胎儿水肿。活产的21例患儿中,20例出生时窒息,21例生后发生呼吸衰竭,20例全身肌无力,19例吞咽困难。29例中,17例(58.6%)为KLHL40基因纯合变异,12例(41.4%)为复合杂合变异。c.1516A>C(p.Thr506Pro)变异�Objective To investigate the clinical,genetic,and pathological features of nemaline myopathy type 8(NEM8)caused by KLHL40 gene variation.Methods The clinical data,gene sequencing results,and musculoskeletal pathophysiology of two cases(a pair of twins)with NEM8 admitted to our hospital in July 2022 were collected.CNKI,VIP,Wanfang,Yiigle,PubMed,Embase,and Web of Science Database were searched with the English and Chinese terms"nemaline myopathy type 8","nemaline body myopathy type 8",and"KLHL40"from January 2007 to February 2023.The clinical,genetic,and musculoskeletal characteristics of the NEM8 cases were summarized using the descriptive statistical analysis method.Results(1)Case report:The mother(G2P2)of the twins(Ⅳ-2 andⅣ-3)was conceived by IVF-embryo transfer and delivered at 37+1 gestational weeks.The two cases were dizygotic twins whose maternal grandmother had lip and palate cleft.The first baby(Ⅳ-1)of the woman exhibited absent left pinna,contracture at the end of both fingers,talipes equinovarus in both feet and died of respiratory failure two hours after birth.Fetal edema and fetal movement delay in the twins and varus right foot in one twin were found during pregnancy.Both cases developed intrapartum asphyxia with the clinical manifestations of generalized muscle weakness,respiratory failure,dysphagia,multiple joint contractures,and fractures.The families withdrew the treatment and the twins died after maintaining life with ventilators for 53 days after birth.Whole exome sequencing of the pedigree found c.1779G>T(p.W593C)homozygous variants of the KLHL40 gene in the twins and c.1779G>T(p.W593C)heterozygous variants of the KLHL40 gene in the parents,both were de novo.Musculoskeletal pathophysiology indicated that muscle fibers are thin and round with a fetal shape and absent rod.(2)Literature review:Among the 29 cases of NEM8,including two current cases and 27 cases retrieved from 15 papers,eight cases terminated the pregnancies,and 21 were live births;seven cases(24.1%)with positive family histor

关 键 词：肌病 杆状体 肌蛋白质类 遗传变异 双生 

分 类 号：R725[医药卫生—儿科]