外显子测序鉴定鳞状毛囊角化病致病基因的研究

Keratosis follicularis squamosa (KFS) is a chronic squamous dermatitis, occasionally accompanied by tumors and/or other abnormalities in organs. Currently, very little is known about the pathogenesis of KFS and no effective treatments are available. Our previous studies have already demonstrated that KFS is an autosomal dominantly inherited disease and mapped the responsible locus in the region of chromosome 7p14.3 - 7p12.1，but the causative gene has not been determined yet. Exome sequencing is a new genomic technique which has been adopted to identify the responsible gene of monogenetic disease by capturing the exome and high throughput sequencing. The aim of this study is to identify the causative gene by exome sequencing and to verify the gene mutation by Sanger sequecing and Real-time quantitative PCR so as to characterize the gene for in-depth understanding of it's function, especially regarding its possible roles in KFS. The results will help elucidate the molecular pathogenesis of KFS. Additionally, this study may lead to the patenting of methods for gene diagnosis and gene therapy of KFS.

鳞状毛囊角化病(KFS)是一种慢性鳞屑性皮肤病，可伴发其它内科疾病或肿瘤，病因不明，且无有效治疗方法。本项目申请者在国际上首次发现KFS呈常染色体显性遗传模式，并已将该病的致病基因定位于染色体7p14.3 - 7p12.1，但致病基因尚未明确。外显子测序是利用外显子捕获系统将全基因组外显子区域DNA捕获并富集后进行高通量测序分析的基因组技术，目前已被成功用于对一些单基因病致病基因的鉴定。本研究拟利用外显子测序技术进一步鉴定KFS的致病基因，并利用Sanger测序和实时定量PCR加以验证，以明确KFS的致病基因，为阐明KFS的分子发病机制及进一步研究该致病基因的功能奠定基础。本研究成果可以为将来的基因诊断和基因治疗提供理论依据，并可能获得具有我国自主知识产权的基因专利。

鳞状毛囊角化病(KFS)是一种慢性鳞屑性皮肤病，可伴发其它内科疾病或肿瘤，病因不明，且无有效治疗方法。本项目申请者在国际上首次发现KFS呈常染色体显性遗传模式，并已将该病的致病基因定位于染色体7p14.3 - 7p12.1，但致病基因尚未明确。本研究拟利用外显子测序技术进一步鉴定KFS的致病基因，并利用Sanger测序和实时定量PCR加以验证，以明确KFS的致病基因。目前已经通过外显子测序分析筛选得到5个候选基因，课题组后续将在相应家系内、散发患者中及200例正常对照中进一步进行验证并分析研究发现的致病基因的功能，从而最终鉴定出KFS的致病基因，为阐明KFS的分子发病机制及进一步研究该致病基因的功能奠定基础。