Purchase this article with an account.
Colin E. Willoughby, Judith Lechner, Wei Jia, Edward W. Dervan, Di Ding, Joanne F. Logan, Sanjoy K. Bhattacharya, Colm J. O'Brien; Mutational Screening Of The Angiopoietin-like 7 Gene In High-tension Primary Open Angle Glaucoma.. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4504.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine whether mutations in angiopoietin-like 7 gene (ANGPTL7) play a role in high pressure glaucoma by performing mutational screening of the ANGPTL7 gene in a cohort of patients with high tension primary open angle glaucoma (POAG).
Glaucoma patients with high tension POAG were recruited following careful phenotyping from the Departments of Ophthalmology in Belfast and Dublin. All patients were Northern European Caucasians from the same geographic area (Ireland). Normal, ethnically and age-matched control subjects were also recruited. All of the 5 coding exons and flanking introns of the ANGPTL7 gene were Sanger sequenced in 70 unrelated patients with high tension POAG and 153 control subjects. Deleterious structural effects of amino acid substitutions on protein function were assessed using a suite of bioinformatics approaches.
Mutational analysis of ANGPTL7 identified a novel missense heterozygous mutation c.299G>T (p. Ser100Ile) and two known SNPs (rs28991002 and rs2076658). The non-conservative substitution (p.Ser100Ile) replaces a highly evolutionary conserved weakly polar hydrophilic serine residue with a non-polar hydrophobic isoleucine residue at position 100 in the coiled coil region of ANGPTL7, and was absent from 153 control individuals (306 chromosomes), dbSNP and the 1000 Genomes Project data. Bioinformatics analysis and molecular modelling predict deleterious functional consequences resulting from the p.Ser100Ile mutation in ANGPTL7.
This is the first study to identify ANGPTL7 mutation in POAG pathogenesis. ANGPTL7 is a potential target for new therapeutic approaches in POAG.
This PDF is available to Subscribers Only