论文部分内容阅读
目的:对1例原因不明发育迟缓伴面部畸形患儿进行分子遗传学分析，明确其致病原因。方法:二代全外显子组测序(whole exome sequencing，WES)筛选符合表型并可能致病的基因变异，应用Sanger测序在患者及其父母中进行变异验证。结果:WES结果显示患儿n KMT2A基因(NM_001197104)存在第15外显子c.4906C>T(p.Arg1636Ter)杂合变异，患儿父母均未检测到该变异，经检索相关数据库及文献均未见报道，为未报道过的新变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南，n KMT2A基因c.4906C>T变异判定为致病性变异(PVS1＋PS2＋PM2＋PP3)。n 结论:KMT2A基因第15外显子c.4906C>T(p.Arg1636Ter)变异可能是这例Wiedemann-steiner综合征患儿的致病原因。新变异的检出扩展了n KMT2A基因变异谱。n “,”Objective:To explore the genetic basis for a child with unexplained global developmental delay (GDD), seizure, and facial deformity.Methods:Whole exome sequencing (WES) was carried out for the patient. Candidate variants were verified by Sanger sequencing of the patient and his parents.Results:WES has revealed that the patient has carried a previously unreported n de novo heterozygous nonsense variant c. 4906C>T (p.Arg1636Ter) of then KMT2A gene, Based on the American College of Medical Genetics and Genomics standards and guidelines, the c. 4906C>T variant ofn KMT2A gene was predicted to be pathogenic(PVS1+ PS2+ PM2+ PP3).n Conclusion:The heterozygous nonsense c. 4906C>T (p.Arg1636Ter) variant of then KMT2A gene probably underlay the disease in the child. Above finding has enriched the spectrum of pathogenic variants of the n KMT2A gene.n