The genetic associations of rhegmatogenous retinal detachment and ectopia lentis

摘要: A genetic predisposition to Rhegmatogenous Retinal Detachment (RD) has been suggested for over 40 years. Ectopia Lentis (EL) is known have a aetiology as part of Marfan Syndrome, other ocular syndromes and when occurring in isolation. This work investigates the these conditions Mendelian non inheritance. The this thesis establishes clear genotype-phenotype correlation between isolated EL its most important causative gene: ADAMTSL4. suggests that mutations gene result more severe phenotype than genes causing EL. In doing so, novel clinical grading system condition also developed. expression ADAMTSL4 distribution protein within tissue investigated further roles development. Modelling was undertaken provides insights future investigations. Traditional next generation investigative tools employed examine families with inherited phenotypes including RD role deleted exon ADAMTS17 identified playing Weill-Marchesani Like syndrome. defined three demonstrated be caused by ADAMTS1 8. previously described few probands ophthalmic phenotypes, delineated gene. It becoming members ADAMTS family proteins play significant Finally, 1300 non-Mendelian were recruited closely phenotyped work. racial differences those affected. cohort contributed significantly towards first genome wide association study (GWAS) into RD; established time contribution condition. Further funding now acquired investigate using exome array. Preliminary quality control analysis performed; allowing platform detailed identify putative functional variants associated RD.