Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls.
Interestingly, this IOP locus is located in close vicinity to the previously widely replicated GLC1G linkage locus for glaucoma, for which subsequent studies have not reached consensus on the causal gene.
We examined the heat shock protein 70/90 (HSP70/90)-organizing co-chaperone stress-induced-phosphoprotein 1 (STI1) as a potential co-modifying gene in glaucoma patients found to harbor WDR36 amino acid variation.
These results demonstrate that, in the correct genetic background, WDR36 sequence variants can lead to an altered cellular phenotype, supporting the theory that WDR36 participates in polygenic forms of glaucoma.
In this study, the prevalence of WDR36 variants was investigated in patients with glaucoma who were of German descent with diverse age of onset and intraocular pressure levels.
In this study, the prevalence of WDR36 variants was investigated in patients with glaucoma who were of German descent with diverse age of onset and intraocular pressure levels.
Screening of the novel WDR36glaucoma-associated gene, which lies centromeric to the disease interval, revealed no mutations within any of the 23 coding exons or splicing junctions.
The strong signal on chromosome 5 lies in the region in which a novel gene, WDR36, in the GLC1G locus was recently identified as causative for adult-onset primary open-angle glaucoma and provides additional evidence that chromosome 5 contains susceptibility loci for glaucoma in multiple human populations.
A mutation in a noncoding region of WDR36 may be responsible for POAG in this family, or another gene in this region may be the actual cause of glaucoma in this family.
The association of WDR36 sequence variants with more severe disease in affected individuals suggests that defects in the WDR36 gene can contribute to POAG and that WDR36 may be a glaucoma modifier gene.