一例点状掌跖角皮病大家系致病基因精细定位

Refined localization of a punctate palmoplantar keratoderma gene in a Chinese family

目的在1例四代点状掌跖角皮病大家系中定位其致病基因所在区域。方法用覆盖8和15号染色体的微卫星标记对一例点状掌跖角皮病大家系进行致病基因的定位研究,用ABI3730测序仪进行微卫星标记的基因分型,利用Linkage软件(5.10 Version)和Cyrillic软件(2.01 Version)进行连锁和单倍型分析。结果该家系符合常染色体显性遗传模式,当外显率为100%时,排除了以前报道过的8q24.13-8q24.21区域,但在15号染色体上的微卫星标记D15S153处获得最大LOD值为5.38(重组率θ=0.00)。单倍型分析将该家系致病基因定位在微卫星标记D15S651和D15S988之间,该结果将国外定位的区域缩小至染色体15q22.2-15q22.31区域之间遗传距离为5.06cm内。结论染色体15q22.2-15q22.31区域存在该点状掌跖角皮病家系的致病基因,表明在中国人群中该病有遗传异质性存在。

Objective To refine the previously mapped regions and identify the disease gene locus in a fourgeneration Chinese family. Methods Genetic linkage analysis was carded out in this family using some microsatellite markers on chromosome 8q and 15q. Two-point linkage analysis was performed using Linkage programs version 5.10 and haplotype was constructed with Cyrillic Version 2.02. Results The authors failed to confirm our previous locus at 8q24.13-8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two-point lod score of 5.38 at D 15S 153 （θ=0.00 ）. Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5.06-cm with the previously reported punctate PPK region. Conclusion Punctate palmoplantar keratodermas （PPK） is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for the punctuate PPK are found to be located on 8q24.13-Sq24.21 and 15q22-15q24 recently. But no genes for this disease have been identified to date. This study refines a disease gene causing punctate PPK to a 5.06-cm interval at 15q22.2-15q22.31.