1例AP2M1基因突变致智力发育障碍伴癫痫发作的遗传特征与临床表型分析  

Clinical phenotype and genetic analysis of Intellectual developmental disorder with seizures caused by AP2M1 gene mutation

作　　者：王丽[1,2] 段丽芬[3] 边成[2] 王梓豪 张艺 褚嘉祐 杨昭庆[2] WANG Li;DUAN Lifen;BIAN Cheng;WANG Zihao;ZHANG Yi;CHU Jiayou;YANG Zhaoqing(Kunming Medical University,Kunming,Yunnan 650500,China;Department of Medical Genetics,Institute of Medical Biology,Chinese Academy of Medical Sciences&Peking Union Medical College,Kunming,Yunnan 650118,China;Epilepsy Center,Kunming Children’s Hospital,Kunming,Yunnan 650034,China)

机构地区：[1]昆明医科大学,云南昆明650500 [2]中国医学科学院/北京协和医学院医学生物学研究所医学遗传学研究室,云南昆明650118 [3]昆明市儿童医院癫痫中心,云南昆明650034

出　　处：《中国优生与遗传杂志》2023年第6期1241-1245,共5页Chinese Journal of Birth Health & Heredity

基　　金：云南省高层次卫生健康技术人才培养专项(L-2018003);云南省科技厅重大科技专项计划(202102AA100021-5);云南省科技厅昆明医科大学应用基础研究联合专项资金面上项目(202001AY070001-273);昆明市卫生科技人才培养项目暨“十百千”工程培养计划(2021-SW(省)-23);灵长类动物模型资源库建立创新工程-重大协同创新项目(2021-I2M-1-024)。

摘　　要：目的分析1例智力发育障碍伴癫痫发作患者的临床表型与遗传学特征,明确患者的临床病因。方法收集患者相关临床资料,采用全外显子组测序对患者及其家系成员进行基因变异筛查,结合既往研究的4例具有相同突变患者的文献报道,分析该基因突变所致的临床表型及遗传特征。结果患儿,女性,4岁10月龄,运动发育迟缓,智力落后伴有癫痫发作情况。患儿脑电图显示弥漫性棘慢波,慢波显著增多。基因检测结果显示患儿AP2M1基因发生c.508C>T(p.Arg170Trp)新发杂合突变。患者父母、哥哥及舅舅基因型为野生型,舅舅有癫痫病史,其他人未见明显临床症状。对国内外相同突变患者的综合分析显示,该基因突变具有不同程度的智力发育障碍、癫痫发作及共济失调等共有表型。结论AP2M1c.508C>T(p.Arg170Trp)基因突变为本例患儿的致病原因。本研究表明中国人中存在该基因突变,进一步丰富了智力发育障碍伴癫痫发作疾病的临床表型谱特征,为该病的临床诊治和遗传咨询提供了更多参考数据。Objective To analyze the clinical phenotypic and genetic characteristics of a patient with intellectual development disorders with seizures,and to identify the cause of disease of the patient.Methods Clinical data were collected,whole exome sequencing technique was used to screen for gene variations of the patient and her family.The clinical phenotypes and genetic characteristics associated with the gene mutation were analyzed in combination with literature reports of other 4 patients with the same mutation in previous studies.Results A 4-years and ten months old girl presented motor retardation,intellectual development disorders and seizures.EEG showed the generalized spike-and-wave,and the slow wave was significantly increased.Whole genome sequencing analysis detected a de-novo missense mutation c.508C>T(p.Arg170Trp)of the AP2M1 gene from the child,however the genotypes of the patient’s parents,brother and uncle were all wild type.The uncle had a history of epilepsy,while the others showed no obvious clinical symptoms.Varying degrees of intellectual development disorders,epilepsy and cerebellar ataxia showed in the patients who carry the same mutation and come from China and other countries.Conclusion The de-novo missense mutation c.508C>T(p.Arg170Trp)of the AP2M1 gene caused the intellectual development with seizures in the proband.This study firstly provides evidence that the disease causing mutation existing in Chinese,and enriches the clinical phenotyps of intellectual development with epilepsy,and provide more reference for clinical diagnosis and genetic counseling of the intellectual developmental disorder with seizures.

关 键 词：智力发育障碍 癫痫 AP2M1基因 基因突变 临床表型 

分 类 号：R725.9[医药卫生—儿科] R742.1[医药卫生—临床医学]