Molecular genetic studies of recessively inherited eye disease

Joyce, Sarah (2011). Molecular genetic studies of recessively inherited eye disease. University of Birmingham. Ph.D.


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Cataract is the opacification of the crystalline lens of the eye. Both childhood and later-onset cataracts have been linked with complex genetic factors. Cataracts vary in phenotype and exhibit genetic heterogeneity. They can appear as isolated abnormalities, or as part of a syndrome.
During this project, analysis of syndromic and non-syndromic cataract families using genetic linkage studies was undertaken in order to identify the genes involved, using an autozygosity mapping and positional candidate approach.

Causative mutations were identified in families with syndromes involving cataracts. The finding of a mutation in CYP27A1 in a family with Cerebrotendinous Xanthomatosis permitted clinical intervention as this is a treatable disorder. A mutation that segregated with disease status in a family with Marinesco Sjogren Syndrome was identified in SIL1. In a family with Knobloch Syndrome, a frameshift mutation in COL18A1 was detected.

Analysis of families with non-syndromic autosomal recessive cataracts was also performed, identifying homozygous candidate regions, and sequencing candidate genes within these regions. The identification of a potential putative mutation in one family in CDC25A illustrated the challenges of distinguishing between rare benign variants and pathogenic mutations.

Identification of novel genes involved in cataractogenesis will increase understanding of the pathways involved in cataract formation, and benefit affected families through genetic counselling, and, potentially personalised management.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine
Funders: Other
Other Funders: Fight for Sight
Subjects: R Medicine > RE Ophthalmology


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