The role of the WDR36 gene on chromosome 5q22.1 in a large family with primary open-angle glaucoma mapped to this region.
OBJECTIVE
To determine whether mutations in the WD40-repeat 36 (WDR36) gene are responsible for primary open-angle glaucoma (POAG) that maps to the GLC1G locus in a family with 16 affected family members.


METHODS
Ninety-two family members underwent clinical evaluation for POAG on the basis of intraocular pressures, cupping of discs, and visual fields after informed consent was obtained. All 23 exons of WDR36 were sequenced in DNA from 5 affected and 2 unaffected family members.


RESULTS
Sixteen family members showed evidence of POAG. A number of sequence variations were identified in family members; most of the variations were previously described single-nucleotide polymorphisms also present in the general population. The 3 new sequence changes were all intronic; 2 were found in only 1 of the family members undergoing screening.


CONCLUSIONS
Several polymorphisms, including known single-nucleotide polymorphisms, were identified; however, none of these were consistent with disease-causing mutations. 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.


CONCLUSIONS
The finding that the WDR36 gene is probably not the responsible gene in this family further documents the genetic heterogeneity of POAG.
Kramer
Patricia L
PL
Departments of Neurology, Molecular and Medical Genetics, and Ophthalmology, Casey Eye Institute, Oregon Health and Sciences University, 3375 SW Terwilliger Boulevard, Portland, OR 97239, USA.
Samples
John R
JR
Monemi
Sharareh
S
Sykes
Renee
R
Sarfarazi
Mansoor
M
Wirtz
Mary K
MK
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics
D005136:Eye Proteins; D022661:RNA, Untranslated; C502341:WDR36 protein, human