遗传性对称性色素异常症ADAR1基因两个新突变

Two novel mutations of the ADAR1 gene associated with dyschromatosis symmetrica hereditaria

目的检测遗传性对称性色素异常症（dyschromatosissymmetricahereditaria，DSH）1个家系和1例散发病例的ADAR1基因突变情况，探讨其发病的分子遗传学机制。方法收集1个DSH家系及1例散发病例的临床资料，提取患者及其正常家系成员外周血DNA，应用PCR反应扩增ADAR1基因的15个外显子编码区及其侧翼序列，通过PCR产物直接测序的方法进行ADAR1基因突变检测。结果在DSH家系患者ADAR1基因的第8外显子检测到c．2638delG（p．Asp880ThrfsX15）移码突变；而DSH散发病例ADAR1基因的第10外显子检测到c．2867C〉A（P．Ser956X）无义突变，经查阅国内外文献两个突变均为未报道过的新突变，100名正常对照未检测出上述两个位点突变。结论ADAR1基因c．2638delG（p．Asp880ThrfsX15）突变和c．2867C〉A（p．Ser956X）突变可能分别是DSH家系和散发病例发病的原因。

Objective To identify potential mutation of the ADAR1 gene in a Chinese family and a sporadic case affected with dyschromatosis symmetrica hereditaria （DSH）. Methods Clinical data and peripheral blood samples from the pedigree and the sporadic patient were collected. Following extraction of genomic DNA, all 15 exons and exon-intron flanking sequences of the ADAR1 gene were amplified by polymerase chain reaction and subjected to direct sequencing. Results A novel frame-shift mutation c. 2638delG （p. Asp880ThrfsX15） from the patients of the pedigree was detected in exon 8 of the ADAR1 gene. And a novel nonsense mutation c. 2867C〉A （p. Ser956X） was detected in exon 10 of the ADAR1 gene from the sporadic case. Neither mutation was identified among the unaffected family members nor 100 unrelated healthy controls. Conclusion The frame-shift mutation c. 2638delG （p. Asp880ThrfsX15） and the nonsense mutation c. 2867C〉A （p. Ser956X） in the ADAR1 gene probably underlie the DSH in our patients.