This collaborative research project between India and Queens University Belfast funded by the British Council for the Prevention of Blindness was divided into three parts: 1. To determine mutalional load of myoGilin (MYOC) in Indian patients with juvenile open angle glaucoma (JOAG). MYOC was sequenced in 22 JOAG patients from Pune, India and 89 controls. A 32 year old female patient with severe JOAG had one previously reported pathogenic (c.1279G>A; p.Ala427Thr) and one novel MYOC mutation (c.1129A>G; p.Thr377 Ala). Cascade screening has identified at risk family members who are under close clinical surveillance. Myocilin genetic testing should form part of the routine clinical care of JOAG patients and their families. 2. Mutational screening of ANGPTL7 a glaucoma candidate gene in primary open angle glaucoma (POAG) and JOAG. ANGPTL7 was sequenced in 166 patients with POAG from Pune and Dublin, 22 patients with JOAG from Pune and 153 age-matched control subjects. A pathogenic mutation c.299G>T (p. Ser100lle) was detected in one Irish patient with POAG. Molecular modeling predicted a deleterious effect, however further work is required to understand the effect of mutant ANGPTL7 on POAG pathogenesis. 3. Massively parallel sequencing of complete mitochondrial genome to determine whether mutations in mitochondrial DNA (mtDNA) play a role in POAG. The complete mitochondrial genome from 32 POAG patients from India and Ireland and controls was amplified by LR-PCR in two fragments and massively parallel sequencing was performed on the Ion PGM™ Sequencer. All variants were confirmed by conventional Sanger sequencing. 50% of POAG cases had a pathogenic mtDNA mutation. 22 mtDNA mutations consisting of T novel mutations and 8 previously reported mutations were identified. 8/22 (36.4%) of these, were In Complex I mitochondrial genes, supporting the concept that mitochondrial dysfundion , specifically Complex I defects, 'play a significant role in POAG .
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:677284 |
| Date | January 2015 |
| Creators | Sambare, Chitra |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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