Clinical Genetics Projects

The Glaucoma Inheritance Study in Tasmania- GIST and the Genetics of Optic Atrophy

Our largest project is the Glaucoma Inheritance Study in Tasmania (GIST) which has been underway for 12 years with more than 2,000 glaucoma patients in over 400 families seen as well as their relatives. We are continuing to examine these families as well as other new families throughout Australia. We have recently begun examining Greek families with branches in Australia and plan to return to examine family members in Greece this year. We are also planning to investigate how many relatives of glaucoma cases have been checked for glaucoma and methods of using family follow up to detect new glaucoma cases. This work has been supported by the ORIA, Glaucoma Australia, Royal Victorian Eye and Ear Hospital research committee, Royal Hobart Research Foundation, Jack Brockhoff Foundation and the NHMRC but we will require new funds to continue.

The aims of GIST are to:

• Identify new glaucoma genes by linkage and association studies
• Establishing the magnitude of the role of individual glaucoma genes and
  mutations
• Examining genotype-phenotype correlations
• Establishing ethnic origins and role of founder effects
• Investigating the natural history of different subgroups of hereditary
  glaucoma
• Evaluating the sensitivity and specificity of clinical examination and
  investigations compared to gene status
• Evaluating of pre-symptomatic genetic testing
• Creating a population, family and genetic database for investigation of new diagnostic and treatment modalities.

Optic atrophy resembles glaucoma and thus we have been looking at modifier genes in large OPA1 families and Leber's Hereditary Optic Neuropathy families.  We have seen more than 500 people in optic atrophy families and continue to look for the modifier genes. Of great importance is the fact that many people in families are carrying the gene and are unaware that they can pass the condition on to their children. Our genetic research has allowed family members to be tested if they would like to pursue.

Twin Study of Glaucoma Screening Parameters

The Twins Eye Study in Tasmania aims to expand the research into the genetics of glaucoma by studying the heredity of clinical parameters used in diagnosing glaucoma.  We have been successful in identifying high heritability of central corneal thickness, intraocular pressure and optic disc cup size.  We are now in the process of identifying the genes responsible for these measures.  We have seen more than 500 pairs of twins in Tasmania and Queensland and plan to see another 500 pairs of twins in Tasmania, Queensland and Victoria over the next two years.This work has been supported by the NHMRC, American Health Assistance Research Foundation, Jack Brockhoff Foundation, RVEEH research committee, Clifford Craig Medical Research Trust and ORIA.

Click here to visit the Twins Eye Study web site

Investigation of Genes Causing Retinal Detachment

Retinal detachment can result in blindness if not diagnosed and treated early. We have helped identify several retinal dystrophy genes and two retinal detachment genes in collaboration with researchers in the United Kingdom. There are however, many families where we have not identified the causative gene mutations and are continuing this work. Of the families with a detachment genes we have been able to identify individuals at high risk of detachment and warn them of the symptoms to be aware of and how to get their eyes checked. This work has been supported by the RVEEH research committee.

Genetics of Congenital Cataract

Cataract is a leading cause of blindness and although amenable to surgery is very problematic in children.  We have identified more than 70 cataract families in South-eastern Australia and have identified the causative gene mutation in around one-third of these families. Our on going collaboration with researchers in Adelaide, Sydney and France will help to identify the genes involved and shed light on the mechanism of cataract formation. This research has been supported by the RVEEH research committee, Perpetual - Ronald Geoffrey Arnott Foundation. The Strabismus Inheritance Study (SIST) and the Identification of the Genes Causing Ptosis.

Strabismus and Ptosis are due to neuromuscular abnormalities, where it appears there is an important genetic component.  Families have been examined in Tasmania and Victoria and in collaboration with Harvard University in the USA we are aiming to identify the genes responsible for two rare but severe forms of strabismus. Identification of the genes associated with various forms of strabismus and ptosis will allow better understanding of the disease mechanism and allow better choice of treatments for patients based on this knowledge. This research has been supported by the Clifford Craig Medical Research Trust, RVEEH research committee, US National Eye Institute.

Identification of Retinal Dystrophy / Retinitis Pigmentosa gene mutations in Australian Families

• Retinal Dystrophies [of which Retinitis Pigmentosa (RP) applies to the largest subgroup] are a group of hereditary disorders where there is loss of vision due to a genetic abnormality affecting the retina. These vary from severe childhood blindness (such as Leber's Congenital Amaurosis) to mild loss of vision (in some cases of RP, Pattern Dystrophy and Best's disease). Many genes have been identified causing RP (autosomal dominant, autosomal recessive and x-linked), as well as Usher Syndrome, Bardet Biedl syndrome, Stargardt's disease, Cone dystrophy, Best's disease, Sorsby's dystrophy, Gyrate Atrophy, Malattia Leventinese/Doyne's dystrophy and others (a full listing of retinitis pigmentosa genes is available at Ret Net). Over the past 10 years we have been involved in research relating to the identification of several of these genes.

This will allow accurate diagnosis, ensuring accurate counselling with specific natural history information.

• It also allows predictive DNA testing to identify those at risk of later developing the disease or being carriers of the disease (particularly X-linked carriers and Incomplete penetrance autosomal dominant carriers.)