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.
| Udar, Nitin; Yellore, Vivek; Chalukya, Meenal et al. (2003) Comparative analysis of the FOXL2 gene and characterization of mutations in BPES patients. Hum Mutat 22:222-8 |
| De Baere, E; Fukushima, Y; Small, K et al. (2000) Identification of BPESC1, a novel gene disrupted by a balanced chromosomal translocation, t(3;4)(q23;p15.2), in a patient with BPES. Genomics 68:296-304 |
