遗传性对称性色素异常症2例ADAR基因突变分析及家系调查

【摘要】 目的 对2个遗传性对称性色素异常症（DSH）家系进行家系调查并基因检测。方法 收集2家系DSH先证者及其家族成员的临床资料，同时采集先证者及其父母和100名无亲缘关系健康对照的外周血标本，应用二代皮肤靶向测序包检测基因突变，再用Sanger测序验证。结果 例1男，双手背、足背5岁时出现散在粟粒大小色素沉着斑和色素减退斑，母亲有类似表现。患者及母亲ADAR基因5号外显子检测到1个新的c.1970dupT（p.F657fs）杂合移码突变，父亲未检测到该突变。例2男，面颈部、腰背部、臀部、双下肢及双手足背夹杂分布米粒至黄豆大小褐色沉着斑和色素减退斑，父亲有类似表现，患者及父亲ADAR基因7号外显子检测到1个已知c.2433_2434delAG（p.T811fs）杂合移码突变，母亲未检测到该突变。无亲缘关系的100例健康对照均未发现上述突变。结论 本研究在DSH患者中检测到1个新的ADAR突变位点c.1970dupT。

Mutation analysis of the ADAR gene in two cases of dyschromatosis symmetrica hereditaria and a survey of their families

【Abstract】 Objective To investigate two Chinese pedigrees with dyschromatosis symmetrica hereditaria （DSH）, and to analyze gene mutations in the pedigrees. Methods Clinical data were collected from two probands with DSH and other family members in their pedigrees. Peripheral blood samples were obtained from the two probands, their parents and 100 unrelated healthy controls. Gene mutations were detected by using a skin-targeted sequencing panel, and then verified by Sanger sequencing. Results Case 1, an 18-year-old male patient, presented with millet-sized hyperpigmented and hypopigmented macules scattered on the dorsum of both hands and feet at the age of 5 years, and his mother had similar manifestations. A novel heterozygous frameshift mutation c.1970dupT （p.F657fs） was identified in exon 5 of the ADAR gene in case 1 and his mother, but not found in his father. Case 2, an 8-year-old male patient, presented with mottled rice- to soybean-sized brown hyperpigmented macules and hypopigmented macules on the face and neck, lower back, buttocks, lower limbs, as well as hands and feet, and his father presented with similar manifestations. A known heterozygous frameshift mutation c.2433_2434delAG （p.T811fs） was identified in exon 7 of the ADAR gene in case 2 and his father, but not found in his mother. Neither of the two mutations was identified in the 100 unrelated healthy controls. Conclusion In this study, a novel mutation c.1970dupT （p.F657fs） in the ADAR gene was identified in a patient with DSH.