一例母系嵌合的Nicolaides-Baraitser综合征患儿的临床特征及基因变异分析

Analysis of clinical characteristics and genetic variant in a child with Nicolaides-Baraitser syndrome due to maternal mosaicism

目的:探讨1例表现为全面发育迟缓、肝功能异常、先天性心脏病、大脑畸形的患儿的基因检测结果,并分析候选变异的致病性。方法:采集患儿及父母外周血标本,提取基因组DNA,进行全外显子组高通量测序,对候选变异进行Sanger测序验证及生物信息学分析。结果:基因检测结果提示患儿SMARCA2基因存在c.2002G>T(p.Glu668Ter)杂合变异,生物信息学分析提示可能致病变异,患儿母亲的外周血基因组DNA中,检测到低比例的嵌合变异,高精度定点检测示变异比例为0.054(246/4549)。结论:该患者被诊断为SMARCA2基因变异引起的Nicolaides-Baraitser综合征,其母存在低比例的嵌合变异。

Objective To carry out genetic testing for a child featuring global developmental delay,abnormal liver function,congenital heart disease,and brain malformation.Methods Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA and trio-whole exome sequencing.Candidate variant was verified by Sanger sequencing.Results Genetic testing revealed that the child has harbored a heterozygous c.2002G>T(p.Glu668Ter)variant of the SMARCA2 gene,which was predicted to be likely pathogenic by bioinformatic analysis.His mother was found to be a low-percentage mosaic for the same variant,with a ratio of 0.054(246/4549).Conclusion The child was diagnosed with Nicolaides-Baraitser syndrome resulting from maternal mosaicism for the SMARCA2 gene variant.