NEXMIF基因新发变异致X-连锁智力低下1例患儿的临床及遗传学分析

Clinical and genetic analysis of a child with X-linked intellectual developmental disorder due to a novel variant of NEXMIF gene

目的分析1例智力障碍、特殊面容患儿的遗传学病因。方法以2023年1月5日就诊于临沂市人民医院的1例智力障碍患儿为研究对象,采集患儿及其父母的外周血以及孕妇的羊水样本,提取基因组DNA,对患儿进行全外显子组测序,用Sanger测序对候选变异进行家系验证。结果全外显子组测序显示患儿携带NEXMIF基因c.1123dupG(p.E375Gfs*4)半合子变异,Sanger测序显示其父母及胎儿均未携带相同的变异。该变异既往未见报道,根据美国医学遗传学和基因组学学会(ACMG)相关指南判断为致病性(PVS1+PS2-P+PM2-P)。结论NEXMIF基因c.1123dupG(p.E375Gfs*4)半合子变异为本研究患儿的致病原因。综合其临床表型和基因检测的结果,患儿被确诊为X-连锁智力发育障碍-98型(XLID98)。上述发现拓展了NEXMIF基因的变异谱,为该家庭的遗传咨询和再生育指导提供了依据。

Objective To explore the genetic basis for a child featuring facial dysmorphism and intellectual disabilities.Methods A child who was diagnosed at Linyi People′s Hospital on January 52023 due to"mental retardation"was selected as the study subject.Peripheral blood samples of the child and his parents,in addition with an amniotic fluid sample from the his mother were collected for the extraction of genomic DNA.Whole exome sequencing was carried out for the child,and candidate variant was verified by Sanger sequencing of his family members.Results The child was found to harbor a hemizygous c.1123dupG(p.E375Gfs*4)variant of the NEXMIF gene,for which both of his parents and the fetus were of the wild type.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was predicted to be pathogenic(PVS1+PS2-P+PM2-P).A healthy infant was subsequently born.Conclusion The hemizygous c.1123dupG(p.E375Gfs*4)variant of the NEXMIF gene probably underlay the disease in this child.Based on his clinical phenotype and genotype,the child was ultimately diagnosed with X-linked intellectual developmental disorder-98.Above finding has also enriched the mutational spectrum of the NEXMIF gene.