Cloning the Gene for Blepharophimosis Syndrome

描述(由申请人提供)：眼球畸形综合征(BPES)，是一种 先天性眼睑畸形，包括临床上的上睑下垂三联症， 水仙花和眼皮包茎。BPES可以零星发生，也可以在常染色体上发生 主导时尚。在类型2的BPES中，异常通常限于 眼皮结构；了解分子遗传扰动 引起这种疾病将导致对正常眼睑形成的理解为 也为更常见的先天性上睑下垂的原因提供了线索。第I类 BPES也与原发性卵巢功能衰竭有关。这个项目的总体目标是 GRANT的应用是确定导致BPES的基因(S)和突变。BPES 最初是由我们实验室通过与染色体3Q连锁定位的。更重要的是 我们已经确定了几名患有BPES的患者，他们的BPES存在微缺失 3号染色体以及在同一染色体上有易位断裂的患者 染色体区域。通过利用这些受试者的DNA，我们已经 确定了BPES基因所在的一个小染色体区域。我们 绘制了关键BPES区域的物理地图。通过确定更多 BPES家系和散发病例的遗传间隔可缩小为 井。该地区的文字记录地图正在编制中。这些基因是 参与修改其他基因的表达，参与 细胞凋亡或在成纤维细胞中表达的基因将特别吸引人 候选人。然后进行突变筛查和DNA直接测序 在受影响的受试者身上进行检测，以筛选突变。这将是 首次分离鉴定出眼皮畸形基因。这个项目将 为NEI计划的目标贡献信息，以“了解 视觉系统是在开发过程中组装的，它的组装会受到怎样的影响 受内生因素和外生因素的影响。

DESCRIPTION (provided by applicant): Blepharophimosis syndrome (BPES), is a congenital eyelid malformation which consists of the clinical triad of ptosis, telecanthus, and lid phimosis. BPES can occur sporadically or in an autosomal dominant fashion. In type 2 BPES, the abnormalities are typically limited to the eyelid structures; understanding the molecular genetic perturbation which causes this disease will lead to an understanding of normal lid formation as well as offer clues into the cause of the more common congenital ptosis. Type I BPES is also associated with primary ovarian failure. The overall goal of this grant application is to identify the gene(s) and mutations causing BPES. BPES was originally mapped by linkage to chromosome 3q by our lab. More importantly we have ascertained several patients who have BPES with micro deletions of chromosome 3 as well as patients with translocation breaks in this same chromosomal region. By utilizing the DNA from these subjects, we have determined a small chromosomal region in which the BPES gene resides. We developed a physical map of the critical BPES region. By ascertaining more families and sporadic cases with BPES, the genetic interval can be narrowed as well. A transcript map of the region is being developed. Genes that are involved in modifying the expression of other genes, genes involved in apoptosis or genes expressed in fibroblasts will be particularly attractive candidates. Then mutation screening and 'direct DNA sequencing will be performed in the affected subjects to screen for mutations. This will be the first isolated eyelid malformation gene identified. This project would contribute information towards the NEI program goal to "understand how the visual system is assembled during development, how its assembly is influenced by endogenous and exogenous factors."