一个表皮松解性掌跖角化病维吾尔家系致病基因研究

目的 对一个维吾尔族表皮松解性掌跖角化病(epidermolytic palmoplantar keratoderma,EPPK)家系角蛋白9基因(keratin 9 gene,KRT9)进行测序,以检测其是否为该病的致病基因.方法 提取新疆地区一个维吾尔族EPPK家系外周血基因组DNA,针对已知候选基因KRT9和KRT1,分别对其所在染色体位置17q12-q21和12q13选取遗传标记进行连锁分析研究,确定连锁区域后,对区域内KRT9基因所有外显子进行测序分析.结果 分别得到48个家庭成员遗传标记的基因型和单倍型,经Linkage软件计算分析,发现标记D17S1787在=0时Lod值达到8.65,并最终将该病候选区域定位于遗传标记17/TG/36620115-D17S846之间约1 Mb范围内.排除该病与位于染色体12q13上的遗传标记DI2S96(θ=0时Lod=-∞)连锁.未发现KRT9基因存在致病性突变.结论 提示该表皮松解性掌跖角化病家系的致病基因位于染色体17q21.2上(chr17:36620083-37146934)约1 Mb区域内,且突变位点不位于KRT9基因编码区.

Mutation analysis of a Uighur family with epidermolytic palmoplantar keratoderma

Objective To map and identify the disease gene for the epidermolytic palmoplantar keratoderma(EPPK)in a Uighur family of China.Methods Blood samples were collected and genomic DNA was extracted from 4 8 members of the Xinjiang Uighur family.Six microsatellite repeat sequences on chromosome region 17q12-q21 and 12q13 were selected based on the two known candidate genes KRT9 and KRT1.Two-point linkage analysis and haplotype analysis were performed.Exons and their flanking intronic sequence of the KRT9 gene were amplified by polymerase chain reaction(PCR)and sequenced.Results Data from the marker D17S1787 suggested linkage and yielded a Lod score of 8.65 at θ=0 by using MLINK software.Genotypes and haplotypes were acquired.The disease gene of the EPPK family is located between markers 17/TG/36620115 and D17S846.Chromosome 12q13 region was excluded with the negative Lod score obtained in marker D12S96(Lod=-∞ at θ=0).No pathogenic mutation was detected in the KRT9 gene.Conclusion The disease gene of the EPPK family is located on chromosome region 17q21.2.The keratin 9 gene might not be the disease gene.