一个遗传性对称性色素异常症家系DSRAD基因剪接位点突变的鉴定

Identification of a novel spfice mutation of DSRAD gene in a Chinese family with dyschromatosis symrnetrica hereditaria

目的 鉴定遗传性对称性色素异常症家系DSRAD基因的突变。方法 收集遗传性对称性色素异常症1个家系成员的血样，提取基因组DNA，用PCR扩增结合直接测序的方法进行DSRAD基因的检测。在内含子区域检测到一个碱基替换后，进一步提取患者外周血RNA，行RT-PCR，直接测序后分析其异常剪接方式。结果在该家系患者的11号内含子区域检测到1个非经典的剪接位点突变，（c．3021—2G〉A），RT-PCR结果发现，12号外显子缺失，在13号外显子处发生移码突变。结论 DSRAD基因11号内含子区域剪接位点突变（c．3021—2G〉A）造成mRNA的异常剪接，导致邻近的12号外显子缺失和13号外显子移码突变，从而引起该家系患者发病。

Objective To detect and validate the mutations of double-stranded RNA-specific adenosine deaminase （DSRAD） gene in a family with dyschromatosis symmetrica hereditaria. Methods Blood samples were collected from the members of a family with dyschromatosis symmetrica hereditaria, and genomic DNA was extracted. PCR and direct sequencing were performed to screen the mutations in DSRAD gene. Then, reverse transcription-PCR （RT-PCR） was used to confirm the characteristics of the mutations in non-canonical splice sites. Results A novel splice mutation, c.3021-2G 〉 A, was identified in the 1 lth intron of the DSRAD gene. As shown by RT-PCR, the 12th exon was deleted, and a frameshifl mutation occurred in the 13th exon. Conclusions The mutation identified in this study, c.3021-2G 〉 A, in the 1 lth intron of DSRAD gene, can cause the abnormal splice of mRNA followed by the deletion of 12th exon and frameshifl mutation in the 13th exon, and result in the development of dyschromatosis symmetrica hereditaria in this family.