基于染色体22q13.1-13.31区域深度测序研究Gorlin综合征的新致病基因

项目名称： 基于染色体22q13.1-13.31区域深度测序研究Gorlin综合征的新致病基因

项目编号： No.31271341

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 陈万涛

作者单位： 上海交通大学

项目金额： 80万元

中文摘要： Gorlin综合征属常染色体显性遗传性疾病，以发育异常和肿瘤易患性为主要特征。不同种族患者的表型和发病机制不尽相同，目前仅在约50%的患者中发现PTCH基因致病突变，偶见PTCH2及SUFU基因突变引发病变，提示该疾病存在其他致病基因。本课题组前期筛查46个患病家系，发现12个家系致病机制不明，遂以其中一个有5代62个成员的大家系为研究对象，定位了与该疾病连锁的染色体区段22q13.1-22q13.31；并完成了对该区段的基因组测序工作。本研究拟在前期研究基础上，通过突变分析及筛选，锁定候选基因，并在其余家系中和散发病例中测序检测、验证该基因的突变情况。在完成候选新致病基因验证后，将对其功能和致病机制开展体内、外系统研究。本项目以遗传家系研究为切入点，旨在获得具有自主知识产权的中国汉人Gorlin综合征新的致病基因，探求中国汉人该遗传病表型特点和分子发病机制，为该疾病的遗传学诊治提供基础。

中文关键词： 口腔癌；痣样基底细胞癌综合征；NOTCH1 基因；PTHLH基因；致病基因

英文摘要： Golin syndrome is an autosomal dominant disorder characterized by a predispostion to neoplasms and developmental abnormalities.Racial predilection in the phenotype and pathogenesis has been observed.Up to date, approximately 50% patients with Gorlin syndrome have mutations in the PTCH gene and mutations in the genes of PTCH2 and SUFU were also detected in one or two cases with this syndrome, which indicates other dominant gene or genes must be involved in causing Gorlin syndrome. Our group have performed mutation screening in 46 pedigrees with this syndrome and found no mutations in these three reported genes in 12 cases.Among these 12 families,a large family with five generations including 62 individuals was chosen as the object of study. A novel Gorlin syndrome locus at chromosome 22q13.1-q13.31 was identified and the genome sequencing for this region was finished. In this study, a candidated gene responsible for this syndrome will be identified by mutation analysis and mutation screening based on the previous data.Then mutations in the candidate gene will be detected in the rest pedigrees without mutations in the known genes responsible for Gorlin syndrome and sporadic cases for verification.After the causative gene is identified, its function and pathogenic mechanisms will be studied in vivo and in vitro sys

英文关键词： oral cancer；nevoid basal cell carcinoma syndrome；NOTCH1；PTHLH；putative gene