CLONING THE GENE FOR BLEPHAROPHIMOSIS SYNDROME

描述：小睑裂综合征（BPES），是一种先天性眼睑 由上睑下垂，内眦赘皮， 和眼睑包茎。 BPES可偶发或常染色体显性遗传 时尚. 因为异常通常局限于眼睑 结构，了解分子遗传扰动， 这种疾病也会导致对正常眼睑形成的理解 为更常见的先天性上睑下垂的病因提供了线索。 因此，本赠款申请的总体目标是映射和克隆 基因突变导致BPES。 BPES最近被绘制成 与染色体3q的连锁 通过确定更多的家庭， BPES法可缩小遗传间隔。 此外，还有几个 已确定3号染色体微缺失的患者， 以及在同一染色体区域有易位断裂的患者。 通过利用来自这些受试者的DNA，将有可能确定一个 BPES基因所在的小的染色体区域。 然后利用外显子 捕获，这将是可能的，以确定候选基因在此 地区 参与改变其他基因表达的基因 (such如锌指基因）或参与细胞凋亡的基因将被 特别有吸引力的候选人。 基因参与成纤维细胞和 结缔组织修饰也是有吸引力的。 然后 逆转录聚合酶链反应（RT-PCR）将用于 受影响的受试者进行突变筛查。 这将是第一个 分离眼睑畸形基因克隆。

DESCRIPTION: 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. Because 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. Therefore the overall goal of this grant application is to map and clone the gene which when mutated cause BPES. BPES has recently been mapped by linkage to chromosome 3q by our lab. By ascertaining more families with BPES, the genetic interval can be narrowed. Additionally, there are several patients which have been ascertained 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, it will be possible to determine a small chromosomal region in which the BPES gene resides. Then by using exon trapping, it will be possible to identify candidate genes within this region. Genes which are involved in modifying the expression of other genes (such as zinc finger gene) or genes involved in apoptosis will be particularly attractive candidates. Genes involved in fibroblast and connective tissue modification will also be appealing. Then reverse-transcriptase polymerase chain reaction (RT-PCR) will be used in the affected subjects to screen for mutations. This will be one of the first isolated eyelid malformation genes cloned.