摘要
目的探讨1例经全外显子组测序(WES)确诊的X连锁智力障碍100型(XLID100)患儿的临床表型及基因变异特征。方法选取2023年9月就诊于南京医科大学附属儿童医院康复科的1例患儿为研究对象, 回顾分析患儿的相关临床资料。采集患儿及其家系成员的外周血样进行WES检测。对检出的候选变异进行Sanger测序验证。根据美国医学遗传学与基因组学学会(ACMG)相关指南, 对候选变异进行致病性评级。查询dbSNP、OMIM、HGMD、ClinVar及gnomAD等数据库, 对候选变异进行分析, 并在Ensembl数据库中查询KIF4A的蛋白质序列, 用Clustal Omega软件进行氨基酸序列保守性分析。对KIF4A基因变异所致XLID100的病例进行回顾。本研究通过了本院医学伦理委员会的审查(伦理号:202402022-1)。结果患儿为3岁6月龄男性, 主要表现为智力障碍、语言发育落后、孤独症、脉络膜囊肿。患儿无特殊面容, 牙齿发育正常, 大运动发育正常无倒退, 无癫痫及热性惊厥史。WES结果显示患儿携带X染色体KIF4A基因c.3385delinsTATC(p.Thr1129delinsTyrPro)变异。Sanger测序证实其母亲和妹妹携带相同的变异, 父亲为野生型。患儿父母外观均无异常。根据ACMG相关指南, 该变异被评定为"意义不明"。该变异在dbSNP、OMIM、HGMD、ClinVar、gnomAD等数据库中均未见收录, 保守性分析提示变异位点正常编码半胱氨酸, 在多个物种中高度保守。文献回顾共检索到6篇相关文献, 涉及27例KIF4A基因变异病例, 其中国内报道仅1例。结论 KIF4A基因c.3385delinsTATC(p.Thr1129delinsTyrPro)变异可能是本研究患儿的遗传学病因。上述发现为该患儿的临床诊断和遗传咨询提供了依据, 同时丰富了KIF4A基因的变异谱。
Objective To explore the clinical phenotype and variants of KIF4A gene associated with X-linked intellectual disability type 100(XLID100)in a child by whole-exome sequencing(WES).Methods A child presented at the Children's Hospital Affiliated to Nanjing Medical University in September 2023 was selected as the study subject.Clinical data of the child was retrospectively analyzed.Peripheral blood samples were collected from the child and his family members for WES analysis.Candidate variant was verified by Sanger sequencing.Pathogenicity of the candidate variant was rated based on the guidelines from the American College of Medical Genetics and Genomics(ACMG).The variant was also searched in dbSNP,OMIM,HGMD,ClinVar and gnomAD databases.Amino acid sequences of the KIF4A protein across various species were retrieved from the Ensembl Genome Browser Database and analyzed using Clustal Omega software.Relevant literature on KIF4A gene mutations associated with XLID1oo was reviewed.This study has been approved by the Medical Ethics Committee of the Hospital(EthicsNo.202402022-1).Results The child,a 3-year-6-month-old male,had manifested intellectual impairment,language delay,autism,and choroid cyst revealed by cranial magnetic resonance imaging.No facial dysmorphism,tooth anomaly,gross motor development delay or regression,and history of seizure and febrile convulsion was noted.WES revealed that he has harbored a c.3385delinsTATC(p.Thrl129delinsTyrPro)variant of the KIF4A gene.Sanger sequencing confirmed that his mother and sister have harbored the same variant,whilst his father was of the wild type.Both of his parents had a normal phenotype.The variant was classified as of uncertain significance based on the guidelines from the ACMG.It was not recorded by the dbSNP,OMIM,HGMD,ClinVar and the gnomAD database.Conservative analysis suggested that the variant site,which normally encodes a cysteine,is highly conserved among various species.A review of the literature had retrieved 6 relevant articles documenting a total of 27 cases of KIF4A gene mutations,with only one case from China.Conclusion The c.3385delinsTATC(p.Thrl129delinsTyrPro)variant of the KIF4A gene probably underlay the XLID100 in this child.Above finding has provided a reference for the clinical diagnosis and genetic counseling and enriched the mutation spectrum of the KIF4A gene.
作者
范晓萱
陈政芳
宣小燕
赵晓科
Fan Xiaoruan;Chen Zhengfang;Xuan Xiaoyan;Zhao Xiaoke(Department of Rehabilitation Medicine,Children's Hospital of Nanjing Medical University,Nanjing Jiangsu 210008,China)
出处
《中华医学遗传学杂志》
2025年第3期307-313,共7页
Chinese Journal of Medical Genetics
基金
国家自然科学基金(81501946)
南京市卫生科技发展专项资金项目(YKK18144)
江苏省妇幼保健协会科研基金(FYX202013)。
关键词
言语和语言发育障碍
智力障碍
KIF4A基因
Speech and language development disorder
Intellectual disability
KIF4A gene
