Hereditary diseases as causes of blindness in Newfoundland: a cohort study with long term follow up

Penney, Colin Blair (2013) Hereditary diseases as causes of blindness in Newfoundland: a cohort study with long term follow up. Masters thesis, Memorial University of Newfoundland.

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Abstract

Background: In 1981, a cohort of 1,013 prevalent cases of blindness, registered with the CNIB, was studied. Established monogenic disease was the cause of blindness in 24% of cases and presumed in a further 6%. Since that original study, considerable new clinical information and family history data have been accumulated. In addition, incident cases with different causes of inherited blindness have been identified. -- Objectives: To determine: the proportion of cases of blindness attributable to monogenic disease after long term follow up; which blindness phenotypes were observed in each geographical region of the province; whether geographic clustering of specific phenotypes occurred; and whether mutation specific disease clustered in particular geographic regions. -- Methodologies: In 2007/8 all cases in the 198 1 cohort were reviewed in order to determine the number in whom the clinical diagnosis had changed; the number in whom the molecular genetic diagnosis was established; and the number of families available for potential novel gene discovery. In addition, the geographic distribution of families with various monogenic causes of blindness was mapped. -- Results: Long term follow up revealed that established genetic disease was the cause of blindness in 30% of the cohort and a further 12% had presumed genetic disease. Geographic clustering was observed with some inherited disorders, and random occurrence of others around the coast of Newfoundland. Within various geographic regions there were multiple genetic causes of blindness. For example, in Conception Bay communities, nine different hereditary eye diseases were identified. -- Conclusions: Newfoundland is a young founder population, consisting of multiple genetic isolates, where the peopling of these isolates has predisposed to the frequent occurrence of hereditary blindness, associated with multiple different genotypes and phenotypes. The genetic architecture of the Newfoundland population has facilitated the identification of novel genes and has resulted in families with the potential to facilitate further identification of novel genes and mutations causing blindness in Newfoundland in the future.

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