【作者】 高敏；

【导师】 张学军； 黄薇； 杨森；

【作者基本信息】 安徽医科大学 ， 皮肤性病学， 2003， 硕士

【摘要】 全基因组扫描定位遗传性对称性色素异常症易感区域 遗传性对称性色素异常症(Dyschromatosis Symmetric Hereditaria，DSH)，又名对称性肢体色素异常症和Dohi对称性肢端色素沉着症。该病是一种少见的遗传性皮肤病。其遗传方式符合常染色体显性遗传，极少数家系符合常染色体隐性遗传。临床上以对称分布的色素脱失和色素沉着的网状斑为特征，好发于婴幼儿期。该病最初由日本人发现并命名。DSH主要见于亚洲人群，日本和朝鲜较多见，意大利和英国等西方国家也有报道。Oyama等曾对185名DSH患者(大部分来自日本)进行总结，发现77.6％患者有家族史，无家族史的散发病例可能是由于自发突变或者不完全外显所致；男女患病之比约为1：1，病情轻重无明显性别倾向；73％患者在6岁之前发病；各国患者的临床表现无显著差异。该病发病机制不明，而且易感区域尚未定位，致病基因还未克隆。我们收集了2个DSH大家系，采取全基因组扫描的方法定位了DSH的易感区域。 目的 确定遗传性对称性色素异常症易感区域。方法 用覆盖全基因组22条常染色体的402个微卫星标记对2个遗传性对称性色素异常症大家系进行全基因组扫描，利用LINKAGE软件(5.10 Version)和CYRILLIC软件(2.02 Version)进行连锁和单倍型分析。结果常染色体显性遗传模式，外显率为100％时，在1号染色体上的微卫星标记D1S2343处获得最大累积连锁值LOD积分为8.85(重组率θ=0.0)，其相邻2个标记D1S2696和D1S2345处的最大LOD积分分别为4.60(重组率θ=0.1)和8.54(重组率θ=0.0)。单倍型分析将易感区域缩小至D1S2696和D1S2635之间11.6cM处。结论染色体1q11-1q21区域存在遗传性对称性色素异常症致病基因。更多还原

【Abstract】 Background Dyschromatosis symmetrica hereditaria (DSH) (OMIM 127400) is also called reticulate acropigmentation of Dohi and symmetric dyschromatosis of the extremities. It is usually transmitted as an autosomal dominant pattern. But DSH has been reported that it could be also transmitted in an autosomal recessive form. It was first described by Toyama in a Japanese family in 1929. To data, most cases of DSH have been reported in the Japanese literature. Occurrence in families of other ethnic origins such as Chinese, Korean, Indian, England and South Americans had also been reported. There were no significant differences in clinical characteristics of the condition between cases from Japan and those from outside Japan. The main features of DSH are asymptomatic small macules scattered on the faces and hyperpigmented and hypopigmented macules on the dorsal aspects of the extremities, which appear in infancy or early childhood. The skin lesions commonly stop spreading before adolescence and last for life. The molecular basis of DSH is unknown. Kono et al. performed linkage analysis between DSH and microsatellite markers on chromosome 9 in three Japanese DSH families. But they obtained LOD scores of < -2 over the whole region of chromosome 9. Thus, they concluded that there was no linkage between DSH and chromosome 9. Up to date, the DSH disease gene and its chromosomal localization have not been identified yet. In this study, we undertook an entire genome-wide scan in two families with DSH identified in Anhui Province in China. Objective To identify a locus for dyschromatosis symmetrica hereditaria. Methods We performed a genome-wide search with 402 microsatellite markers in two large Chinese families to map the chromosome location of the responsible gene.LINKAGE software (5.10 Version) snd CYRILLIC software (2.02 Version) were used for linkage and haplotype analyses.Results We identified a locus at chromosome 1q11-1q21 with a cumulative maximum two-point LOD score of 8.85 at D1S2343 (9=0.00). Haplotype analyses indicate that the disease gene is located within 11.6cM region between markers D1 S2696 and D1 S2635. This is the first locus identified for the DSH. This study provides a map location for isolation of a disease gene causing DSH.Conclusion Chromosome 1q11-1q21 contains the disease gene of dyschromatosis symmetrica hereditaria. This is the first locus identified for the DSH. This studyprovides a map location for isolation of a gene causing DSH.更多还原