Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma.
OBJECTIVE
To determine the distribution of WDR36 sequence variants in a cohort of patients with primary open-angle glaucoma (POAG) in the United States.


METHODS
All of the 23 coding exons and flanking introns of the WDR36 gene were sequenced in 118 probands from families with at least two members affected by POAG, 6 probands from juvenile-onset POAG families, and 108 control individuals.


RESULTS
Thirty-two WDR36 sequence variants were found in this population of patients with POAG. Nonsynonymous single-nucleotide polymorphisms (SNPs), including those previously described as "disease-causing" and "disease susceptibility," were found in 17% of POAG patients and 4% of control subjects. Although the distribution of WDR36 variants in the pedigrees did not show consistent segregation with the disease, the WDR36 sequence variants were found more frequently in patients with more severe disease.


CONCLUSIONS
The results of this study suggest that abnormalities in WDR36 alone are not sufficient to cause POAG. 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.
Hauser
Michael A
MA
Center for Human Genetics, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA.
Allingham
R Rand
RR
Linkroum
Kevin
K
Wang
Jun
J
LaRocque-Abramson
Karen
K
Figueiredo
Dayse
D
Santiago-Turla
Cecilia
C
del Bono
Elizabeth A
EA
Haines
Jonathan L
JL
Pericak-Vance
Margaret A
MA
Wiggs
Janey L
JL
D000328:Adult; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D007438:Introns; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D005136:Eye Proteins; C502341:WDR36 protein, human