Novel gene for adult-onset primary open-angle glaucoma

May 3

- Fort Lauderdale, FL - WDR36 is a novel causative gene for adult-onset primary open-angle glaucoma (POAG) that is located at the GLC1G locus. According to the lead author, Sharareh Monemi, MD, of the University of Connecticut, mutations in this gene are involved in the etiology of high- and low-pressure POAG. Dr. Monemi described the study at the annual meeting of the Association for Research in Vision and Ophthalmology on Monday.

The authors had previously mapped the adult-onset POAG locus to 5q and sought to specifically identify the GLC1G disease-causing gene. They carried out DNA genotyping and data analysis, and new POAG families were linked to the 5q22.1 region. The investigators also carried out mutation screening by direct DNA sequencing of coding exons and the flanking intron-exon boundaries.

Dr. Monemi reported that the new POAG locus was mapped between D5S1466 and D5S180. Additional studies provided linkage in seven families DS51480 and DS52051. Seven genes mapped between DS51480 and DS52051 underwent mutation screening, and one significant alteration (D658G) was found in WD40-repeat 36 (WDR36).

"This mutation segregated in all seven affected members of our first GLC1G-linked family and was absent in 470 normal control chromosomes. Further screening found 24 DNA variations in 130 unrelated POAG subjects. We identified four evolutionary conserved disease-causing mutations, specifically N355S, A449T, R529Q, and D658G, in 17 subjects; 65% of these had high-pressure glaucoma and 35% had low-pressure glaucoma," she said.

WDR36 gene expression was identified by reverse transcriptase-polymerase chain reaction in the sclera, lens, ciliary muscle, ciliary body, trabecular meshwork, and iris.