一例Menkes病患儿的基因变异分析

目的对一例疑诊Menkes病患儿进行临床和遗传学分析。方法提取患儿及其父母基因组DNA,行家系全外显子测序及多重连接探针扩增技术检测ATP7A基因微重复、缺失,对疑似致病变异行生物信息学分析,并对患儿及其父母行一代测序验证变异位点。结果在受检者ATP7A基因发现c.1870-13T>G的核苷酸变异,为新发剪切变异。结论该患儿为ATP7A基因c.1870-13T>G变异而导致Menkes病,家系全外显子测序为表型异质性强的遗传性疾病提供了有力工具。

Genetic analysis of a male infant with Menkes disease

Objective To carry out genetic testing for a male infant suspected for Menkes disease.Methods Genomic DNA of the proband and his parents were extracted and subjected to family trio whole-exome sequencing(WES).Microduplication and microdeletion of the ATP7A gene were detected by multiplex ligation-dependent probe amplification(MLPA).Suspected variants were subjected to bioinformatic analysis and verified by Sanger sequencing.Results The proband was found to harbor a de novo c.1870-13T>G variation of the ATP7A gene,which may alter a splice site and affect its protein product.Conclusion The patient was diagnosed with Menkes disease due to the c.1870-13T>G variant of the ATP7A gene.Whole-exome sequencing of family trios is a powerful tool for the diagnosis of diseases with strong phenotypic heterogeneity.