Genetic testing for glaucoma: lessons learned from translational genetic research and implications for genetic counselling

Author: Emmanuelle Souzeau

Souzeau, Emmanuelle, 2017 Genetic testing for glaucoma: lessons learned from translational genetic research and implications for genetic counselling, Flinders University, School of Medicine

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My original contribution to knowledge includes the delineation of the phenotypes associated with known glaucoma genes, the identification of novel glaucoma genes and the study of the ethical and psychological implications of genetic testing and counselling for glaucoma. There is currently a gap in knowledge regarding the role of genetic counselling in glaucoma. Genetic counselling can have a significant impact on patients and their families through discussing genetic testing and results, modes of inheritance, risk for family members and future children, and helping patients and their families adapt to the psychological implications of the genetic contribution to the disease. Glaucoma is a leading cause of irreversible blindness worldwide, with devastating implications for individuals if not diagnosed and treated appropriately. The aetiology of glaucoma is genetically heterogenous: both Mendelian and multifactorial inheritance occur, and the condition can affect all ages, from newborns to adults, each with their own implications for families. Through the publications included in this thesis, I investigated the monogenic causes of glaucoma and the benefits of the provision of genetic counselling. I demonstrated that MYOC and CYP1B1 variants associated with primary open-angle glaucoma were more prevalent in individuals with severe disease, I reported on the characterisation of novel variants and I contributed to the delineation of phenotypes associates with TBK1 duplications in primary open-angle glaucoma. I contributed to the identification of novel genes for primary congenital glaucoma (TEK) and nanophthalmos (TMEM98), I reported on the glaucoma prevalence and phenotype associated with FOXC1 & PITX2 variants and the contribution of FOXC1 towards primary congenital glaucoma. Finally, I investigated participants’ experience of predictive genetic testing for MYOC glaucoma, the benefits of predictive genetic testing in minors for childhood-onset MYOC glaucoma and the ethical implications of incidental findings from genetic testing. The genetic heterogeneity and the phenotypic overlap in glaucoma justifies a targeted gene panel approach using high throughput sequencing technologies to confirm or refine the clinical diagnosis based on medical and familial information. Precision medicine to tailor prevention and treatment plans based on an individual’s genetic results is an appealing strategy, especially considering that preventative and restorative therapies are under development for glaucoma. Identifying at-risk individuals based on molecular diagnosis is becoming critically important in the context of clinical trials for targeted therapies, and disease registries such as the Australian and New Zealand Registry of Advanced Glaucoma can greatly facilitate the recruitment process. Current research directions in glaucoma highlight a role for genetic counsellors in translational genetic research. My work contributed towards a framework for genetic counselling in glaucoma through the incorporation of translational research outcomes to provide the best genetic counselling and genetic testing options to patients and their families.

Keywords: Genetic counselling, glaucoma, genetic testing, translational genetic research

Subject: Medicine thesis

Thesis type: Doctor of Philosophy
Completed: 2017
School: School of Medicine
Supervisor: Jamie Craig