CASK基因移码变异致智力障碍伴小头畸形2例患儿的临床与遗传学分析  

Genetic and clinical analysis of two children with mental retardation and microcephaly due to a frameshifting variant of CASK gene

作　　者：刘苏娟 王莹莹 黄后艳 徐萍 姜晔 周陶成 Liu Sujuan;Wang Yingying;Huang Houyan;Xu Ping;Jiang Ye;Zhou Taocheng(Department of Traditional Chinese Medicine,Anhui Children′s Hospital,Hefei,Anhui 230051,China)

机构地区：[1]安徽省儿童医院中医科,合肥230051

出　　处：《中华医学遗传学杂志》2024年第9期1090-1095,共6页Chinese Journal of Medical Genetics

基　　金：安徽省科技厅课题(1804h08020254);安徽省红十字基金会课题(2022ZYZD03)。

摘　　要：目的报道2例智力障碍伴小头畸形患儿,分析其临床表型与遗传学特征,明确其可能致病原因。方法选取2例分别在2021年3月12日和2021年6月22日就诊于安徽省儿童医院的患儿为研究对象,收集患儿的临床资料,采集患儿及其父母外周静脉血样,对患儿进行染色体分析及全外显子组检测。对候选变异进行Sanger测序家系验证,并分析其致病性。本研究通过安徽省儿童医院医学伦理委员会的审查(EYLL-2018-008)。结果2例患儿的染色体核型分析与拷贝数检测均未见异常。全外显子组测序发现患儿携带CASK基因c.471delT(p.Pro157Profs*9)移码变异,患儿2携带CASK基因c.1259_1269delCTGAGAATAAC(p.Pro420fs*27)移码变异。经Sanger测序验证,上述2个变异均为新发。根据美国医学遗传学与基因组学学会与分子病理学协会(ACMG-AMP)相关指南,上述2个变异均被评级为致病性(PVS1+PS2+PP3)。结论CASK基因新发变异可能是上述2例患儿的主要致病原因。ObjectiveTo explore the clinical and genetic characteristics of two children with mental retardation and microcephaly.MethodsTwo children who had visited the Anhui Children′s Hospital respectively on March 12 and June 22,2021 were selected as the study subjects.Peripheral venous blood samples were collected from them and their parents,and subjected to chromosomal karyotyping and whole exome sequencing analyses.Candidate variants were verified by Sanger sequencing and pathogenicity analysis.This study was approved by the Anhui Children′s Hospital(Ethics No.EYLL-2018-008).ResultsChromosomal karyotyping and copy number detection of the two children had found no abnormality.Whole exome sequencing revealed that child 1 has harbored a c.471delT(p.Pro157Profs*9)frameshifting variant of the CASK gene,whilst child 2 has harbored a c.1259_1269delCTGAGAATAAC(p.Pro420fs*27)frameshifting variant of the CASK gene.Sanger sequencing confirmed that both variants were de novo in origin.Based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology(ACMG-AMP),both variants were rated as pathogenic(PVS1+PS2+PP3).ConclusionThe de novo variants of the CASK gene probably underlay the pathogenesis of mental retardation and microcephaly in both children.

关 键 词：CASK基因 智力障碍 小脑发育不全 小头畸形 

分 类 号：R725.9[医药卫生—儿科]