遗传性对称性色素沉着症1例患儿的遗传学分析

Genetic analysis of a child with Dyschromatosis symmetrica hereditaria

目的探讨1例ADAR1基因变异所致的遗传性对称性色素沉着症(DSH)患儿的临床及遗传学特征。方法选取2020年6月因"手背不规则色素斑疹"就诊于郑州大学第一附属医院皮肤科的1例DSH患儿作为研究对象,收集家系成员的临床资料。对患儿进行全外显子组测序(WES),并用Sanger测序进行家系验证。进一步采用SWISS-MODEL预测野生型及变异型蛋白的三级结构。结果患儿为13岁男性,手背存在对称性色素沉着和色素脱失斑,临床诊断为DSH。WES及Sanger测序结果显示患儿及其父亲ADAR1基因第10外显子均存在c.2858dup(p.T954Dfs*20)杂合变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为致病性变异(PVS1+PM2_Supporting+PM1+PP3)。结论ADAR1基因c.2858dup(p.T954Dfs*20)变异可能是该DSH患儿的遗传学病因。

Objective To investigate the clinical and genetic features of a child with Dyschromatosis symmetrica hereditaria(DSH)and variant of the ADAR1 gene.Methods A child who was admitted to the Department of Dermatology of the First Affiliated Hospital of Zhengzhou University in June 2020 due to irregular pigmented maculopapular rash on the dorsum of hands was selected as the study subject.Whole exome sequencing(WES)was carried out for the child and his similarly affected father,and Sanger sequencing was used to verify the candidate variant.SWISS-MODEL was used to predict the secondary and tertiary structures of the wild-type and mutant ADAR1 proteins.Results The child,a 13-year-old boy,had symmetrical hyperpigmented and depigmented spots on the back of his hands and was clinically diagnosed with DSH.WES and Sanger sequencing results showed that he and his father had both harbored a heterozygous c.2858dup(p.T954Dfs*20)truncating variant in exon 10 of the ADAR1 gene.Based on the guidelines from the American College of Medical Genetics and Genomics,the variant was predicted as pathogenic(PVS1+PM2_Supporting+PM1+PP3).Conclusion The c.2858dup(p.T954Dfs*20)variant of the ADAR1 gene probably underlay the DSH in this pedigree.