摘要
目的:探讨1例KDM6B基因变异相关神经系统发育障碍患儿的临床及遗传学特征。方法:回顾性分析2021年7月郑州大学附属儿童医院收治的1例KDM6B基因变异相关神经系统发育障碍患儿的临床资料,总结其临床表现及基因变异特点并进行文献复习。结果:患儿男性,1岁6个月,存在前额突出、关节松弛、远端骨骼异常,行为、认知、语言、智力及精神运动发育落后。全外显子组测序及Sanger测序结果显示KDM6B基因第11外显子存在c.1718delC(p.Pro573Hisfs*9)新发杂合移码变异。根据美国医学遗传学与基因组学学会和分子病理学会指南,该变异被判定为致病变异(PVS1+PS2+PM2_supporting),既往未见报道。文献复习未检索到相关中文文献;检索到英文文献4篇,共报道98例患者,加上本例患儿共有99例KDM6B基因变异相关神经系统发育障碍患者,主要表现为语言、运动、行为异常、智力障碍等神经系统发育障碍,以及面部畸形、肌张力低下、婴儿期喂养困难/胃食管反流、关节/韧带松弛、手脚趾/掌异常等。共发现83个变异位点,包括37个移码变异、18个错义变异、21个无义变异、7个剪接变异。结论:KDM6B基因变异可引起神经系统发育障碍、颅面发育及骨骼异常,KDM6B基因新发杂合变异考虑为本例患儿的遗传学病因。本研究扩展了KDM6B基因变异谱。
Objective To investigate the clinical and genetic characteristics of KDM6B gene variation associated neurological developmental disorder in a child.Methods Clinical data were collected from a child of KDM6B gene variation associated neurological developmental disorder admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2021.His clinical manifestations and genetic variation profiles were retrospectively analyzed and literature review was conducted.Results The patient was a one-year-six-month old male,with protruding forehead,joint laxity,distal skeletal abnormalities,and behavioral,cognitive,language,intellectual,and psychomotor development disorder.The whole-exome sequencing and Sanger sequencing confirmed that there was a de novo heterozygous frameshift variation c.1718delC(p.Pro573Hisfs*9)in exon 11 of the KDM6B gene.This variation was classified as pathogenic(PVS1+PS2+PM2_supporting)according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines,with no prior reports.By literature review,no relevant Chinese literature was retrieved,whereas 4 English literatures were found,reporting 98 patients,totally 99 patients(including this case)with nervous system development disorder due to KDM6B gene variation.The main manifestations were neurodevelopmental disorders such as speech,motor,and behavioral abnormalities,mental retardation,as well as facial deformities,hypotonia,infantile feeding difficulties/gastroesophageal reflux,joint/ligament laxity,and abnormalities of the hands and toes/palms.A total of 83 variation sites were found,including 37 frameshift variations,18 missense variations,21 nonsense variations,and 7 splicing variations,all of which were heterozygous variations.Conclusions The KDM6B gene variation can lead to neurodevelopmental disorder,craniofacial developmental and skeletal abnormalities.The de novo heterozygous variation in the KDM6B gene is considered to be the genetic etiology of this child.This study extends the spectrum of KDM6B gene variant.
作者
张利明
刘磊
杨建伟
孙红启
杨志晓
杨俊梅
Zhang Liming;Liu Lei;Yang Jianwei;Sun Hongqi;Yang Zhixiao;Yang Junmei(Department of Clinical Laboratory,Children's Hospital Affiliated to Zhengzhou University,Zhengzhou Key Laboratory of Children's Infection and Immunity,Zhengzhou 450018,China;Pediatric Medical Institute,Children's Hospital Affiliated to Zhengzhou University,Henan Provincial Key Laboratory for Genetic and Metabolic Disease in Children,Zhengzhou 450018,China;Department of Neurology Children's Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China)
出处
《中华神经科杂志》
2025年第11期1205-1210,共6页
Chinese Journal of Neurology
基金
河南省医学科技攻关计划联合共建项目(LHGJ20240560)。
