TY - JOUR
T1 - Comprehensive sequencing of the myocilin gene in a selected cohort of severe primary open-angle glaucoma patients
AU - O’Gorman, Luke
AU - Cree, Angela J.
AU - Ward, Daniel
AU - Griffiths, Helen L.
AU - Sood, Roshan
AU - Denniston, Alastair K.
AU - Self, Jay E.
AU - Ennis, Sarah
AU - Lotery, Andrew J.
AU - Gibson, Jane
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Primary open-angle glaucoma (POAG) is the most common form of glaucoma, prevalent in approximately 1–2% of Caucasians in the UK over the age of 40. It is characterised by an open anterior chamber angle, raised intraocular pressure (IOP) and optic nerve damage leading to loss of sight. The myocilin gene (MYOC) is the most common glaucoma-causing gene, accounting for ~2% of British POAG cases. 358 patients were selected for next generation sequencing (NGS) with the following selection criteria: Caucasian ethnicity, intraocular pressure (IOP) 21–40 mm Hg, cup:disc ratio ≥0.6 and visual field mean deviation ≤−3. The entire MYOC gene (17,321 bp) was captured including the promoter, introns, UTRs and coding exons. We identify 12 exonic variants (one stop-gain, five missense and six synonymous variants), two promoter variants, 133 intronic variants, two 3′ UTR variants and 23 intergenic variants. Four known or predicted pathogenic exonic variants (p.R126W, p.K216K, p.Q368* and p.T419A) were identified across 11 patients, which accounts for 3.07% of this POAG cohort. This is the first time that the entire region of MYOC has been sequenced and variants reported for a cohort of POAG patients.
AB - Primary open-angle glaucoma (POAG) is the most common form of glaucoma, prevalent in approximately 1–2% of Caucasians in the UK over the age of 40. It is characterised by an open anterior chamber angle, raised intraocular pressure (IOP) and optic nerve damage leading to loss of sight. The myocilin gene (MYOC) is the most common glaucoma-causing gene, accounting for ~2% of British POAG cases. 358 patients were selected for next generation sequencing (NGS) with the following selection criteria: Caucasian ethnicity, intraocular pressure (IOP) 21–40 mm Hg, cup:disc ratio ≥0.6 and visual field mean deviation ≤−3. The entire MYOC gene (17,321 bp) was captured including the promoter, introns, UTRs and coding exons. We identify 12 exonic variants (one stop-gain, five missense and six synonymous variants), two promoter variants, 133 intronic variants, two 3′ UTR variants and 23 intergenic variants. Four known or predicted pathogenic exonic variants (p.R126W, p.K216K, p.Q368* and p.T419A) were identified across 11 patients, which accounts for 3.07% of this POAG cohort. This is the first time that the entire region of MYOC has been sequenced and variants reported for a cohort of POAG patients.
UR - https://www.scopus.com/pages/publications/85062411131
U2 - 10.1038/s41598-019-38760-y
DO - 10.1038/s41598-019-38760-y
M3 - Article
C2 - 30816137
AN - SCOPUS:85062411131
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3100
ER -