GNB5基因变异致智力发育障碍伴窦房结功能障碍一家系并文献复习  

Intellectual developmental disorder with cardiac arrhythmia syndrome in a family caused by GNB5 variation and literature review

作　　者：麦嘉卉 欧振恒 陈黎[1] 段婧[1] 廖建湘[1] 韩春锡[1] Mai Jiahui;Ou Zhenheng;Chen Li;Duan Jing;Liao Jianxiang;Han Chunxi(Department of Neurology,Shenzhen Children′s Hospital,Shenzhen 58038,China;Department of Cardiology,Shenzhen Children′s Hospital,Shenzhen 518038,China)

机构地区：[1]深圳市儿童医院神经内科,518038 [2]深圳市儿童医院心血管内科,518038

出　　处：《中华儿科杂志》2020年第10期833-837,共5页Chinese Journal of Pediatrics

基　　金：深圳市医疗卫生三名工程(SZSM201812005)。

摘　　要：目的总结GNB5基因变异致智力发育障碍伴窦房结功能障碍综合征(IDDCA)的临床特点及遗传学分析。方法收集深圳市儿童医院神经内科2018年9月确诊的IDDCA一家系的临床资料,提取患儿及亲属的外周血DNA进行遗传学分析及验证。以“GNB5”“IDDCA”“LADCI”和“智力发育障碍伴窦房结功能障碍综合征”“言语发育落后、注意缺陷多动或认知障碍、伴或不伴窦房结功能障碍综合征”为关键词分别查阅在线人类孟德尔遗传数据库(OMIM)和PubMed数据库及中国知网(CNKI)数据库、万方数据库自建库至2020年3月相关文献报道,并结合本家系进行智力及运动发育、癫痫、心律等临床资料和遗传学分析总结。结果先证者男,11月龄,表现为全面发育迟缓及抽搐,伴肌张力减低,窦性停搏,脑电图、视觉诱发电位均异常,提示为IDDCA。二代测序基因检测发现患儿携带GNB5基因纯合移码变异c.136delG(p.Glu46Argfs*8),父母均为杂合变异。先证者兄4岁8月龄,临床表现类似,基因验证结果与先证者一致。文献检索相关病例报道7篇(均为英文),共报道14个GNB5基因变异家系(27例患者),包括本家系2例共29例患者,诊断年龄为5.5月龄~23岁,男11例(38%)、女18例(62%),表现为IDDCA有20例(69%),表现为言语发育落后、注意缺陷多动或认知障碍,伴或不伴窦房结功能障碍综合征有8例(28%)。患者中66%(19/29)出现智力障碍,41%(12/29)诊断癫痫,79%(23/29)出现语言发育障碍,62%(18/29)出现窦房结功能障碍。GNB5基因复合杂合变异3个家系4例,纯合变异12个家系25例(86%),其中8个家系17人为近亲结婚;共检测到12种GNB5基因变异,其中无义变异4种、移码变异3种、错义变异2种、剪切变异2种、同义变异导致的剪切错乱1种。结论GNB5基因变异所致IDDCA主要表现为全面发育迟缓或严重的智力障碍、窦房结功能障碍等。GNB5基因相关综合征存在表型异质性,以�Objective To explore the clinical characteristics of intellectual developmental disorder with cardiac arrhythmia syndrome(IDDCA)in a family caused by GNB5 gene variation and to review the literature.Methods The clinical and genetic data of an infant with IDDCA,who visited Shenzhen Children′s Hospital in September 2018,were collected and analyzed.His parents′and brother′s gene analysis was also done by the next-generation sequencing and confirmed by Sanger sequencing.Related literature up to March 2020 was searched in Online Mendelian Inheritance in Man(OMIM),PubMed,CNKI and Wanfang databases with“GNB5”“IDDCA”“LADCI”“intellectual developmental disorder with cardial arrhythmia”“language delay and attention deficit-hyperactivity disorder or cognitive impairment with or without cardiac arrhythmia”as the key words.The related papers were retrieved and analyzed to summarize the clinical and genetic characteristics of this disorder.Results The proband was an 11-month-old boy who presented with mental and motor developmental retardation,accompanied with convulsion and muscle weakness.Sinus arrest was also detected.His electroencephalogram(EEG)and flash visual evoked potential(FVEP)were both abnormal.Genetic analysis identified the homozygous frameshift variation of GNB5 gene(c.136delG,p.Glu46Argfs*8)in this infant and heterozygous variation in his parents,confirmed the diagnosis of IDDCA.The same GNB5 variation was identified in his brother,who was 4 years and 8 months old and had developed the similar clinical manifestations after birth.There were only 7 papers reporting this disease in the literature review,with a total of 27 patients from 14 families.Including these 2 cases,there were 29 patients in total,whose age of diagnosis ranged from 5.5 months to 23 years.Among all the patients,20 cases(69%)were diagnosed as IDDCA,while 8 cases(28%)as LADCI;and 11(38%)were males while 18(62%)females.Regarding the clinical features,66%(19/29)had mental retardation,41%(12/29)had seizures,79%(23/29)develo

关 键 词：癫痫 基因 GNB5 智力障碍 病窦综合征 

分 类 号：R748[医药卫生—神经病学与精神病学]