Cloning the Gene for Blepharophimosis Syndrome

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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."