A Second Locus for Pigment Dispersion Syndrome Maps to Chromosome 18q21

Abstract

Abstract: : Purpose: Glaucoma associated with pigment dispersion (GPDS) is the most common form of glaucoma affecting the young adult population. Approximately 50% of individuals affected with pigment dispersion develop glaucoma associated with elevated intraocular pressure and degeneration of the optic nerve. In humans, GPDS is inherited as an autosomal dominant trait, while similar syndromes in mice exhibit more complex inheritance patterns. We have previously mapped one locus for this condition to chromosome 7q36, and have also identified pedigrees that do not demonstrate linkage to this region indicating genetic heterogeneity. The purpose of this study is to perform a genome–wide scan using GPDS families that are not linked to 7q36 to identify the location of additional genes responsible for this syndrome. Methods: 38 family members from a large pedigree (pedigree 559, 14 affected) and 17 members (11 affected) from three smaller families were identified for this study. All pedigree members underwent a complete ocular examination and pigment dispersion syndrome was defined as characteristic pigment deposition on the corneal endothelium as well as in the trabecular meshwork, and iris transillumination defects. All pedigree members were genotyped using two hundred thirty–eight microsatellite repeat markers. Two point lod scores assuming an autosomal dominant model were calculated using the FASKLINK computer package. Because of the possibility of reduced penetrance, lod scores were calculated for all pedigree members and for affected pedigree members only. Results: A maximum two–point lod score of 7.8 was obtained for marker D18S1144 on18q21 using all pedigree members (affected and unaffected). A significant lod score of 4.2 was obtained for marker D18S1144 using only affected pedigree members. Haplotype analysis identified a 12 cM critical region extending from marker D18S1119 to D18S483, using critical recombination events in affected family members from pedigree 559. Consistent haplotypes segregating with the disease were also identified in the three smaller pedigrees. Conclusions: These results provide evidence for a new locus responsible for pigment dispersion syndrome on chromosome 18q21. A number of interesting candidate genes with ocular expression are located within the 18q21 region and are currently being screened for causative mutations.

Keywords: gene mapping • genetics