遗传性对称性色素异常症一家系致病基因的定位和突变研究

目的 探讨遗传性对称性色素异常症家系的致病基因。方法 明确先证者的临床诊断后,收集该家系成员的血样抽提基因组DNA,应用基因分型和连锁分析的方法进行基因定位,并对该定位区域内DSRAD基因直接测序,分析其突变位点。结果 基因分型和连锁分析将该家系的致病基因定位于1号染色体,和已知报道的区域一致。突变研究发现该家系所有患者的DSRAD基因2号外显子均携带CAA→TAA的突变,使得517位氨基酸由谷氨酰胺变成中止密码子。结论 该遗传性对称性色素异常症家系中的患者存在DSRAD基因的无义突变。

Identification of DSRAD Gene Mutation in a Chinese Dyschromatosis Symmetrica Hereditaria Family

Objective To identify the gene locus and the mutation of DSRAD (double-stranded RNA adenosine deaminase) in a Chinese dyschromatosis symmetrica hereditaria(DSH) family. Methods After confirming the diagnosis of the DSH proband, the genomic DNA was extracted from the whole blood samples of every members of the pedigree. The DSRAD gene intervals were localized by linkage analysis and haplotype reconstruction. The mutation of DSRAD was detected by direct sequencing. Results The candidate gene was localized at the 1q region, consistent with the reported region. The direct sequencing results showed that there was a CAA→TAA transition at exon 2 of DSRAD in all affected family members, which consequently led to a nonsense mutation of Gln517Ter. Conclusion A nonsense mutation is found in the Chinese DSH family.