一个ARX基因变异导致的智力障碍家系遗传学分析

Genetic analyzing for a Chinese intellectual disability pedigree with ARX gene mutation

目的对一个智力障碍家系进行临床表征及基因变异分析,并探讨其发病的分子机制。方法先证者因智力障碍于2019年12月就诊于漯河市中心医院,收集家系4人外周血,采用全外显子测序对先证者和家系成员进行致病基因变异筛查,选取有临床意义的变异位点;采用PCR反应和Sanger测序对变异位点进行验证分析,并结合有关数据库对变异位点进行分析。结果全外显子测序结果筛查到ARX基因c.1162A>G(p.Lys388Glu)与该家系患者表型共分离。Sanger测序结果与外显子组测序结果一致,母亲为该变异的携带者。该变异在健康人群中无突变频率报道,且多种生物信息学软件预测为有害突变,结合OMIM数据库表型分析,ARX基因c.1162A>G(p.Lys388Glu)导致的表型与患者表型吻合。结论ARX c.1162A>G(p.Lys388Glu)可能是导致该家系患者智力障碍的原因,该变异在国内尚未见报道。

Objective To investigate the molecular mechanism of the disease based on the clinical characterization and genetic mutation analysis in a family with intellectual disability.Methods The proband with intellectual disability was diagnosed at Luohe Central Hospital in December 2019.Peripheral blood samples were collected from four family members.Whole exome sequencing(WES)was used to screen the pathological mutations.Then the PCR and Sanger sequencing were used to verify the selected mutations and combine the relevant database to analyze variation loci.Results We infer that the ARX c.1162 A>G was co-segregated with the phenotype of the family based on the results of WES.The results of sanger sequencing and WES are consistent.The mother of the proband is the carrier of the mutation.There is no mutation frequency reported in the healthy population.The mutation of the ARX c.1162A>G is harmful inferred by a variety of bioinformatics software.Combined with the phenotypic analysis of OMIM database,we infer the phenotype caused by the mutation is consistent with the patients in the family.Conclusion The mutation of the ARX c.1162 A>G may be the cause of the intellectual disability in the family affected.And the variant has not been reported in China.