Cloning the Gene for Blepharophimosis Syndrome

描述（由申请人提供）： 睑裂综合征 (BPES) 是一种 先天性眼睑畸形，包括上睑下垂的临床三联征， 外眦赘皮和眼睑包茎。 BPES 可以偶发发生或以常染色体形式发生 主导时尚。在 2 型 BPES 中，异常通常仅限于 眼睑结构；了解分子遗传扰动 这种疾病的原因将导致对正常眼睑形成的理解 并为更常见的先天性上睑下垂的病因提供线索。 Ⅰ型 BPES 还与原发性卵巢功能衰竭有关。本次活动的总体目标 拨款申请的目的是确定引起 BPES 的基因和突变。 BPES 最初由我们的实验室通过与染色体 3q 的连锁进行定位。更重要的是 我们已经确定了几位患有 BPES 的患者，其中 3 号染色体以及该染色体易位断裂的患者 染色体区域。通过利用这些受试者的 DNA，我们 确定了 BPES 基因所在的一个小的染色体区域。我们 绘制了关键 BPES 区域的物理图。通过确定更多 BPES家族和散发病例，遗传区间可缩小为 好吧。该区域的转录图谱正在开发中。基因是 参与修饰其他基因的表达，参与基因 成纤维细胞中的细胞凋亡或基因表达将特别有吸引力 候选人。然后突变筛选和“直接 DNA 测序”将 在受影响的受试者中进行突变筛查。这将是 首次分离出眼睑畸形基因。该项目将 为 NEI 计划目标“了解如何 视觉系统在开发过程中组装，其组装受到怎样的影响 受内源性和外源性因素的影响。”

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."