两个遗传性对称性色素沉着症家系的ADAR1基因变异分析

Analysis of ADAR1 gene variants in two pedigrees affected with dyschromatosis symmetrica hereditaria

目的检测两个中国汉族遗传性对称性色素沉着症家系(dyschromatosis symmetrica hereditaria,DSH)ADAR1基因的变异位点。方法收集家系成员的临床资料和血样,应用PCR扩增结合Sanger测序法对两家系的先证者ADAR1的外显子进行基因变异分析,待疑似致病变异确定后,对其他家系成员进行相应位点的验证。同时选取100名与本家系无关的正常人作为对照。结果Sanger测序结果显示家系1先证者及先证者父亲ADAR1基因存在第11外显子c.3002G>C(p.Asp968His)杂合变异。家系2先证者及先证者儿子ADAR1基因存在第12外显子c.3145C>T(p.Gln1049Ter)杂合变异。检索文献发现,两种变异均为未报道过的新变异,100名健康对照均未发现上述变异。结论ADAR1基因c.3002G>C(p.Asp968His)和c.3145C>T(p.Gln1049Ter)变异可能分别为两个DSH家系的疑似致病变异。

Objective To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria(DSH).Methods Clinical data and peripheral blood samples of the pedigrees were collected.All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing.Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls.Results For pedigree 1,Sanger sequencing has identified a heterozygous missense variant c.3002G>C(p.Asp968His)in exon 11 of the ADAR1 gene in the proband and his father.For pedigree 2,a novel nonsense variant c.3145C>T(p.Gln1049Ter)was identified in exon 12 of the ADAR1 gene in the proband and his son,which were previously unreported and absent among the healthy controls.Conclusion The c.3002G>C(p.Asp968His)and c.3145C>T(p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.