IGENE(S) FOR PRIMARY CONGENITAL GLAUCOMA

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DESCRIPTION: Primary Congenital Glaucoma (PCG) is an autosomal recessive disorder caused by unknown developmental defect(s) of the trabecular meshwork and anterior chamber angle. Although PCG is the most common form of glaucoma in infancy, nothing secure is known about its specific ambryologic pathogenesis despite studies of various animal models. Furthermore, although a single chromosomal assignment has been proposed there is no method to detect carriers by any clinical, biochemical or molecular techniques. Therapy is primarily surgical with variable success, as more than one surgical intervention might be necessary to control intraocular pressure in a number of these patients. Thus, there is significant morbidity associated with both this condition and the currently available treatment options. The investigators will apply genetic an physical mapping strategies to isolate the gene(s) for PCG. Two complementary linkage approaches to gene mapping will be used: outbred family linkage studies of the "sib pair" method and homozygosity mapping. The latter approach will utilize consanguineous Saudi Arabian pedigrees. Alternative strategies for initial gene localization will include: (I) allele-frequency dependent homozygosity mapping (AHM) and (ii) pooling of genomic DNA samples from affected and unaffected individuals in single large pedigrees. Other traditional mapping approaches to be use for positional cloning include YAC contig building, PFGE mapping, eye cDNA library screening, and exon trapping. Mutation scanning detection methods including heteroduplex analysis, chemical cleavage of mismatched bases, SSCP analysis, DGGE, and direct DNA sequencing will then detect specific mutations. The identification of a PCG gene has potent implications for both ocular and human development and have the potential to improve the quality of life of the affected individuals. Further, it will enable the accurate identification of siblings who may be carriers of the condition, and has the ultimate capacity to modify or prevent the devastating visual consequences of this disorder in future generations.