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Title: An investigation into the genetic basis of primary angle-closure glaucoma
Author: Low, S.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2013
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Primary angle-closure glaucoma (PACG) is a common cause of irreversible blindness worldwide but the epidemiology varies significantly between races. This thesis describes the clinical and genetic examination of families with primary angle-closure suspect (PACS) and more advanced disease. Participants were mainly of European origin, from 101 families. Parametric, non-parametric and quantitative trait linkage analyses, a pilot case-control study and targeted gene screening were performed. In the largest PACG family recruited, two promising regions on chromosomes 10 and 13 were identified. Phenotype-genotype correlation highlighted plateau iris to be the most prominent feature in affected individuals, although shorter axial biometry and hyperopic refractive error were also observed. Quantitative trait linkage applied to a number of traits measured by anterior segment optical coherence tomography provided support for the chromosomes 10 and 13 loci. Maximum iris thickness and adjusted axial length at the chromosome 10 region showed LOD score of 1.3 and 1.5 respectively. Adjusted anterior chamber depth and lens vault on chromosome 13 showed LOD scores of 1.7. As the linkage results were suggestive but not conclusive, a pilot case-control study, followed by participation in an international consortium-led genome wide association study (GWAS) was performed. Three single nucleotide polymorphisms, rs1015213, rs3753841 and rs11024102, were found to be associated with cases of acute angle closure (AAC) and PACG. The loci for our family based analyses and the GWAS did not overlap. In 13 families, PAC was found in probands but further clinical and genetic examination of family members identified atypical features. Angle-closure was often observed as part of a more complex ocular phenotype that led to syndromic diagnoses of Noonan, Marfan, Weill-Marchesani, Ehlers-Danlos and Bestrophinopathies. In conclusion, PACG is a multifactorial disease. Phenotypic predisposition such as plateau iris has a small number of genetic contributors, but advanced disease has further contributions from common SNPs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available