Absence of myocilin and optineurin mutations in a largePhilippine family with juvenile onset primary open angle glaucoma

[摘要] Purpose: To analyze the role of the two primary open angle glaucoma(POAG) genes, myocilin (MYOC) and optineurin (OPTN), ina large Philippine family segregating autosomal dominant juvenile onsetopen angle glaucoma (JOAG).Methods: The coding sequences of the MYOC and OPTN geneswere screened in 27 family members by polymerase chain reaction anddirect sequencing. The specific MYOC promoter polymorphism(MYOC.mtl) was identified by restriction endonuclease assay. All ofthe ABI MD-10 microsatellite markers on chromosomes 1, 2, 3, 7, 8, and10, which harbor the six known POAG loci, were analyzed for linkage withPOAG.Results: No mutation was identified in this large kindred. Instead,three polymorphisms (-80G->A, -1000G->C, R76K) in MYOC andfour polymorphisms (T34T, M98K, R545Q, IVS7+24G->A) in OPTN werefound. All markers flanking the six known POAG loci gave LOD scores notmore than 1.1. Non-parametric linkage analysis for all these markersresulted in p values more than 0.05.Conclusions: Both mutation testing and linkage analysis providestrong evidence against MYOC and OPTN being the causative genein this large family. It indicates that unidentified genes will underliethe occurrence of glaucoma in this family.

[学科分类] 生物化学/生物物理