The WDR36 Gene on Chromosome 5q22.1 Is Not Responsible for POAG in a Large Family That Maps to This Region

Abstract

Purpose: : Identifying mutations within the genes related to adult Primary Open–Angle Glaucoma (POAG) may provide important clues to the mechanism of disease. One such gene is the WD40–Repeat 36 (WDR36) located within the GLC1G locus on chromosome 5q. We had previously mapped a large POAG family to the GLC1G locus. We screened DNA from this family for mutations in the 23 exons of WDR36.

Methods: : One multigenerational Dutch POAG family was enrolled in the study. The family consisted of 92 members, of which 16 individuals (9 males, 7 females) were affected with POAG. Linkage was previously reported in this family following a genome–wide linkage scan. All 23 exons of the WDR36 gene were sequenced in a subset of seven family members (5 affected, 2 unaffected). Direct sequencing was conducted with A BL–Big Dye Terminator Cycle kit and run on an ABI–3100 Genetic Analyzer and DNA Sequencer. Primers were designed to flank the intron–exon boundaries of the genes selected for mutation screening.

Results: : None of the four predicted or the three potential disease–causing mutations identified by Monemi et al (Hum.mol.genet., 2005 14:725) occurred in any of these seven individuals. Several previously reported polymorphisms were identified in this family, yet none of these met the accepted criteria for disease–causing status.

Conclusions: : It is possible that mutations in non–coding regions in WDR36, for example splice sites or promotors, are responsible for POAG in this family. It is also possible that the occurrence of POAG in this family is the result of mutations in another gene in the region. Therefore, in addition to the other six genes in the 2 Mb region of linkage identified by Monemi et al (Hum.mol.genet., 2005 14:725), we are sequencing genes upstream in the adjacent 4.6 Mb region that encompasses the critical linkage region for this family.

Keywords: genetics • gene mapping • mutations