The genetic characterization of mendelian ocular disorders in the population of Newfoundland and Labrador

Doucette, Lance P. (2012) The genetic characterization of mendelian ocular disorders in the population of Newfoundland and Labrador. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Background -- Recently, ocular genetics have shown the first successes in genetic therapies, and treatment of genetic diseases making identification of disease genes of great importance. Gene discovery is most successful through the study of genetic founder populations, such as that of Newfoundland and Labrador. -- Objective -- The objective of this thesis was to identify disease genes in three forms of Mendelian ocular disease: anterior segment dysgenesis (ASD), achromatopsia (ACHM), and microphthalmia-dwarfism (MDW). This was undertaken to find novel genes and mutations to further our understanding genetic pathways involved in each condition. -- Results -- Of the 11 families recruited for this study, 8 were solved through identification of pathogenic variants. The ASD phenotype was discovered to be caused by a novel mutation in FOXE3, seven ACHM families through mutations in CNGA3 and CNGB3, one ACHM family was found to actually have a rare disease called Jalili Syndrome through a novel mutation in CNNM4, and two MDW families helped determine a putative disease locus on 16q21. -- Conclusions -- The identification of seven mutations (two novel, five previously described) have solved the genetic etiology in eight of eleven families providing insight into the disease pathways for these families. This allows for genetic counseling and the possibility for genetically based therapies in the future.

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