Purchase this article with an account.
B. F. Hogewind, K. Gaplovska-Kysela, T. Theelen, G. H. Yam, F. P. C. Cremers, C. B. Hoyng, A. Mukhopadhyay; Sequence Analysis of MYOC & CYP1B1 in Familial Primary Open Angle Glaucoma Patients From the Netherlands. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5590.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to identify causal mutations and/or disease-associated variants in MYOC and CYP1B1 in familial POAG cases from the Netherlands.
The inclusion criteria for the patients were an age of onset of more than 35 years, an intra ocular pressure of more than 22 mm Hg, glaucomatous optic neuropathy in both eyes, visual field loss consistent with assessed optic neuropathy in at least one eye, an open anterior chamber at gonioscopy, and at least two other affected first-degree family members. The exons of MYOC and CYP1B1 were sequenced in probands from 30 ‘unrelated’ families with multiple POAG patients. The identified sequence variants were examined in the family and screened among 250 unrelated controls. A novel disease-causing mutant was expressed in CHO-K1 cells and protein secretion and solubility were analyzed.
Two different MYOC mutations were found in three families. One family harbours the p.Q368X mutation and a novel mutation (p.F430L) was found in two other families. The novel mutation was not present in 250 unrelated Dutch controls. The functional assay showed that, unlike wild-type MYOC, the mutant protein was secretion-incompetent and became detergent-insoluble. For the p.Q368X mutation, the level of transcripts is being analysed in the fibroblasts obtained from patients. Mutational analysis of CYP1B1 has not resulted in any putative causal variant so far.
This is the first study to identify the genetic defects in Dutch POAG patients. Two MYOC mutations were found in three families, one of which represents a novel missense variant. The mutant protein was shown to be non-secreted in vitro. The result will help to further understand the genetic variations in POAG pathogenesis.
This PDF is available to Subscribers Only