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Research

Retinal Degeneration

Project Principal Investigators: Prof. Raj Ramesar (Research), Emeritus Prof. Jacquie Greenberg (Diagnostics)

Scientific Officer (Project leader): Dr. Lisa Roberts (Research and Diagnostics)

Research Nurse: Sr. Gameda Benefeld

PhD Student: Ms. Stacey Moses 

MSc (Genetic Counselling) Student: Ms Monica Araujo

BSc (Hons) Student: Ms. Nicole Midgley

Intern: Ms. Safiye Yildiz

 

The Retinal Research Group

Back L – R: Dr Lisa Roberts, Ms Safiye Yildiz, Ms Nicole Midgley, Ms Monica Araujo

Front L - R: Prof Jacquie Greenberg, Prof Raj Ramesar, Sr Gameda Benefeld

L – R: Dr Lisa Roberts, Prof Raj Ramesar, Prof Jacquie Greenberg

RESEARCH

The research into inherited retinal disorders (IRDs) in Southern Africa involves the characterisation of the genetic basis of inherited blindness. Our research to date has led us to identify three novel genes – PRPF8, CA4, and IDH3A. We have also found the causative gene defects (mutations) in many South African families with IRDs, in many other genes. We have noticed in the 20 years since the research project was started, that the most prevalent genetic defects in the USA & the UK are present in South Africans at an almost insignificant incidence, indicating a novel gene pool for this group of disorders.

The identification of the specific mutation (and understanding of its biology) in every individual with an inherited IRD in SA, should provide the basis for establishing a solid foundation for the management of families with these genetic eye conditions and eventually, for possible future treatment options.

Early identification and management may be the key to delaying the onset of the serious blinding complications of some of these IRDs. Patients who know their status and understand their disease are well placed to receive training, while still sighted, for the years of visual impairment which remain ahead. Furthermore, patients who know their specific gene mutation have an established route to receive medical assistance, and are the most likely to benefit from timeous intervention. Knowing the exact mutation causing the blindness is an absolute prerequisite to participate in any gene-based therapy clinical trials.

We research the following IRDs interchangeably, moving our research focus every few years depending on international findings and technological advances: Retinitis Pigmentosa (dominant, recessive and X-linked forms), Macular Degeneration (including Stargardt disease), Leber Congenital Amaurosis and Usher syndrome.

Our current research includes:

–  Detection of mutations which cause IRDs, using Next Generation Sequencing /targetting screening platforms; via Asper Ophthalmics, The Manchester Centre for Genomic Medicine/ Manchester University , through various research collaborations, and locally with our own Ion Torrent platform.

– Analysis of hypomorphic and complex mutations of the ABCA4 gene in South Africans 

– Screening of the mutation hotspot, ORF15, of the RPGR gene in South Africans

– Understanding the molecular pathogenesis of mutations in the CA4  and PRPF8 genes

TO PARTICIPATE IN THE RESEARCH PROGRAMME

Written informed consent has to be obtained from all individuals before any research can be undertaken. To enquire about participating in the research programme, please contact Prof. Jacquie Greenberg or Retina South Africa.  Please note the forms below that need to accompany all samples that are sent to the UCT laboratory.

There is no guarantee that by participating in the research programme, a family’s genetic mutation(s) will be identified. We do, however, endeavour to translate any diagnostic results arising from the research to participants (see point E below).

DIAGNOSTIC TESTING

Research testing costs were historically covered by the research programme, funded by Retina SA, and undertaken at UCT. Genetic counselling and testing costs will no longer be covered by the research programme. Individuals can be seen for referral and counselling via the state services or as private referrals at their own cost, and the genetic test results will only be issued in the diagnostic setting outlined below. NO research results will be reported on. Genetic counselling and diagnostic testing costs will not be covered by the UCT research programme (since 2013). Costs are to be borne by the individual concerned and must be discussed up front. Arrangements must be made for payment of the testing costs before the blood is sent to the laboratory, in accordance with Retina SA’s protocols. Testing may also be arranged through other laboratories at the request of the counsellor and/or patient. However, it needs to be noted that other laboratories may need extra time to prepare for the necessary testing.

Three types of diagnostic testing are available:

a) Asper targetted screening:  Mutation screening can be performed by Asper Ophthalmics, in Estonia (Europe), as part of a diagnostic screening process. This takes approximately 3 months as all meaningful Asper results are verified at UCT prior to result delivery. For information about this testing option, please contact Retina South Africa.

b) Manchester NGS (Next Generation Sequencing) of >170 IRD genes: The Manchester Centre for Genomic Medicine/ Manchester University  NHS Trust in the UK offers sequencing of a panel of >170 IRD genes. This takes approximately 5 months. Sequencing results are interpreted by a multidisciplinary team of experts in Manchester, and reports are generated for result delivery by local genetic counsellors. For information about this testing option, please contact Retina South Africa.

c) “Quick 7” testing: Our previous research indicated that there are seven common mutations in South African individuals of Afrikaner descent  who suffer from Stargardt disease. We have established that about 5% of individuals in this demographic group are carriers of these mutations. Testing for these seven mutations (namely the "Quick 7" test ) is available directly via the National Health Laboratory Service (NHLS). The Quick 7 test takes about 6 weeks and is only offered to Stargardts patients of Afrikaner ancestry. Approximately 40-50% of these patients are molecularly diagnosed using this test. The test is less effective in other populations or for other IRDs. For information about this testing option, please contact Retina South Africa

d) BBS10 founder mutation screening: Bardet Biedl syndrome (BBS) is a multisystem disorder, characterised by IRD, obesity, polydactyly and intellectual disability. In South Africa, BBS in indigenous African patients is often due to a single founder mutation in the BBS10 gene. Testing for this specific mutation is available directly via the National Health Laboratory Service (NHLS)

e) Diagnostic testing arising from the research programme (testing for a known familial mutation): Once a genetic mutation has been identified through the research, and is confirmed, that family can be offered diagnostic testing for their specific mutation, at a cost. Given that the exact mutation is known, this is a much simpler process and consequently, the cost is considerably less than when mutation screening has to be performed, as in (a) and (b) above.

The diagnostic testing, and then the delivery of genetic results to individuals, is according to a very strict protocol, as follows:

  1. If contactable, all individuals who gave blood for research (or in the case of minors, the guardian) are sent a letter that the research found something meaningful for the family and if they would like to have a diagnostic genetic test, it is now available. Family members who have not participated in the research programme will not be contacted (as there will be no contact details available). Passing on the available information becomes the responsibility of the family members who did participate in the research.  An individual may contact UCT to see if results are available but no research results will be released in the form of a written report.
  2. If they would like to have more information about the research or request a diagnostic genetic test (affected, at-risk, or carrier testing), an appointment is made to see a genetic counsellor at UCT/Wits/Groote Schuur Hospital as part of the routine state genetic services or they can be seen in private sector, at their own cost. The genetic test results will only be issued in the diagnostic setting, as outlined above.
  3. A new blood sample will be required from all individuals for diagnostic genetic testing. The relevant testing should be requested through UCT/NHLS/private laboratory. Genetic testing can be undertaken at UCT by arrangement, via Retina South Africa and takes about 6 weeks.
  4. An appointment is made for post-test genetic counselling, and the results will then be delivered to the individual, in person. Individuals are requested to provide permission for their results to be released to their managing clinical team. A copy of the DNA report can then be sent to the clinician; either by the genetic counsellor or by Professor Greenberg.