CHAMP1基因变异所致常染色体显性智力障碍40型患儿1例的分析  

Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene

作　　者：徐菁晗 李晶晶[1] 焦智慧[1] 孙阁阁 陈铎[1] 孔祥东[1] 王莉[1] Xu Jinghan;Li Jingjing;Jiao Zhihui;Sun Gege;Chen Duo;Kong Xiangdong;Wang Li(Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,郑州450002

出　　处：《中华医学遗传学杂志》2023年第1期47-52,共6页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002203)。

摘　　要：目的探讨1例CHAMP1基因变异所致常染色体显性智力障碍40型(MRD40)患儿的临床表型和遗传学特征。方法选取2019年10月至2020年9月于郑州大学第一附属医院就诊的1例MRD40型患儿为研究对象。采集患儿的临床资料,用低深度高通量全基因组拷贝数变异测序(CNV-seq)和全外显子组测序(WES)对其进行遗传学分析,并回顾文献报道的CHAMP1基因变异所致MRD40病例的临床表型和遗传学特征。结果患儿,女,11月龄,表现为全面发育迟缓合并特殊面容。CNV-seq检测未见异常,WES结果提示其携带CHAMP1基因c.1908C>G(p.Y636*)新发杂合变异。连同12篇文献报道的33例患儿,除发育迟缓、智力障碍外,大多存在肌张力减退(94.1%)、说话和/或行走时间延迟(85.2%,82.4%)及眼部异常(79.4%)。共检出CHAMP1基因变异26个,大多为功能缺失变异,位于第3外显子且为新发。结论CHAMP1基因c.1908C>G(p.Y636*)杂合变异可能是本例患儿的致病原因。对于全面发育迟缓/智力障碍、肌张力减退伴特殊面容的患儿,应尽早进行基因检测以明确病因。Objective To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40(MRD40)due to variant of the CHAMP1 gene.Methods Clinical characteristics of the child were analyzed.Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing(CNV-seq)and whole exome sequencing(WES).A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants.Results The child,a 11-month-old girl,has presented with intellectual and motor developmental delay.CNV-seq revealed no definite pathogenic variants.WES has detected the presence of a heterozygous c.1908C>G(p.Y636*)variant in the CHAMP1 gene,which was carried by neither parent and predicted to be pathogenic.Literature review has identified 33 additional children from 12 previous reports.All children had presented with developmental delay and mental retardation,and most had dystonia(94.1%),delayed speech and/or walking(85.2%,82.4%),and ocular abnormalities(79.4%).In total 26 variants of the CHAMP1 gene were detected,with all nonsense variants being of loss-of-function type,located in exon 3,and de novo in origin.Conclusion The heterozygous c.1908C>G(p.Y636*)variant of the CHAMP1 gene probably underlay the WRD40 in this child.Genetic testing should be considered for children featuring global developmental delay,mental retardation,hypertonia and facial dysmorphism.

关 键 词：常染色体显性智力障碍40型 CHAMP1基因 发育迟缓 全外显子组测序 

分 类 号：R725.9[医药卫生—儿科]