Newsletters
July 2009
Genes for Health Conference
The Genes for Health conference was held from 2–6 May 2009. Genes for Health was GRaPH-Int’s inaugural conference, which was combined with the HGSA’s 33rd annual scientific meeting. As Professor Fiona Stanley said in her opening address, “The aims of the HGSA and GraPH-Int professional organisations are complementary – to promote professional interaction, genetic education and training, communication and public engagement, public policy development, research and knowledge transfer into clinical practice.”
Prior to the Conference, there were Special Interest Group meetings of the Australasian Association of Clinical Geneticists, Australasian Society of Genetic Counsellors, Australasian Society of Cytogeneticists and the Molecular Genetics Society of Australasia. The conference attracted over 300 delegates from Australia and New Zealand and included 28 international delegates. There were 169 abstracts received and 28 were invited for oral presentations. Highlights of the Conference were the Sutherland Lecture by Professor Andrew Sinclair and the HGSA Oration by Dr Ian Walpole. An entertaining debate was moderated by Dr Cyril Mamotte between Professor Wylie Burke and Associate Professor Martin Delatycki on “Should we screen for HFE-associated Hemochromatosis?” Overall, the program generated much discussion and a number of links between national and international organisations for future work in public health genomics have been established. We are pleased to acknowledge the financial support of The University of WA, Curtin University of Technology, Edith Cowan University and our silver sponsors – Biomarin, Roche Diagnostics and Genzyme.
The Office of Population Health Genomics conference presentation abstracts and posters are available on our publications page.
Folate Monitoring Survey
Mandatory fortification of food with folate is due to commence in September 2009.
OPHG is co-coordinating studies in the Aboriginal and non-Aboriginal population to measure blood folate and vitamin B12 levels and dietary intake of folate prior to September. The study will be repeated in 3-4 years time so we can measure the effect of mandatory fortification.
The Aboriginal component of the study is being conducted in collaboration with Broome Regional Aboriginal Medical Service, Derbarl Yerrigan Health Service, Western Diagnostic Pathology, Telethon Institute for Child Health Research and the School of Population Health – The University of Western Australian.
The non-Aboriginal component of the study is being conducted in collaboration with Western Diagnostic Pathology, Telethon Institute for Child Health Research and the School of Population Health – The University of Western Australian.
Evaluation of Prenatal Screening and Diagnosis in Western Australia 2005–06.
Data for this project have been collected and linked together and are now in the process of being analysed, so that we can evaluate the performance of the program, particularly in regard to identification of Down Syndrome, and compare against other States and countries. The data will also give us a more complete picture of the uptake of first trimester screening, second trimester screening and diagnostic testing and a picture of the population who don’t participate in the program.
Project partners include:
- Western Diagnostic Pathology
- General Pathology
- PathWest at Princess Margaret and King Edward Memorial Hospitals, Department of Cytogenetics and Clinical Biochemistry Antenatal Screening Laboratory
- Attadale Hospital
- Geraldton Radiology
- Goldfields Medical Centre – Xray West
- Imaging the South
- Joondalup Radiology
- Kalgoorlie Regional Hospital Ultrasound
- King Edward Memorial Hospital Ultrasound
- Obstetric and gynaecological ultrasound
- Park Ultrasound
- Perth Radiology
- Pilbara Radiology
- Quinns Medical Imaging
- SKG Radiology
- Swan District Hospital Ultrasound Department
- Women’s Imaging Services
- Western Ultrasound for Women
- The X Ray Place
Familial Hypercholesterolaemia (FH) Cascade Screening
Following the UK NICE Guidelines and building on our experience with the FHWA project, it is likely that DNA-based diagnosis of FH will become increasingly important for the unambiguous identification of adult FH heterozygotes and cascade screening for affected individuals in their extended families. The FH Special Interest Group of the Atherosclerosis Society of Australasia has been developing a Model of Care, based on the document developed in Western Australia as a partnership program involving academics, clinicians, Royal Perth Hospital and the Health Department of WA for the screening and management of FH (Watts GF, Dimmitt S, Redgrave T, Bates T, Emery J, Burnett J, van Bockxmeer F, Poke S, Maxwell S, O’Leary P, Powell M, Southwell L. Familial Hypercholesterolaemia. Perth Western Australia 2008). The pilot program is funded as one of nine Flagship Projects of the Commonwealth Government’s “Australian Better Health Initiative”.
DNA cascade screening for FH
The main challenges for population screening for FH at a DNA level are the costs and feasibility of screening patients suspected to have FH, even with current high throughput DNA sequencing technology. Approximately 95% of FH cases are caused by mutations in the Low Density Lipoprotein receptor (LDLR) gene, with the remainder being due to defects in the APOB gene rendering LDL incapable of binding to its receptor. Up to 1 % of cases are due to gain-of-function defects in the PCSK9 gene that interferes with normal intracellular catabolism of LDL. Although more than 1000 mutations have been reported, it now appears that 9–15% of FH cases cannot be detected by conventional exon by exon sequence analysis which misses large duplications and deletions in the LDLR. A commercial kit for detecting this type of “copy number variation” in the LDLR based on Multiplex Ligation Probe Amplification (MLPA) has been developed by MRC-Holland. However, both these techniques are expensive methods not suitable for large scale population screening. In 2008, Progenika (Spain) and TEPNEL (UK) have respectively developed commercial array (LIPOCHIP) and multiplex ARMS (Elucigene FH20) assays for FH. These protocols detect mutations in the LDLR, APOB and PCSK9 genes that are known to occur commonly.
The protocol adopted for the WA cascade screening program is based on the sequential application of both the Elucigene FH20 and the MLPA kits followed by complete exon by exon sequence analysis of the LDLR gene. The results obtained with the first 120 cases diagnosed on clinical grounds to be FH using Dutch Lipid Clinic Scores (DLC) show that with a DLC score of 8 or higher (“definite FH”), detection of causative mutations occurred in 4 out of 5 patients, with the success rate dropping off markedly with lower scores. The Elucigene FH20 kit together with MLPA could detect a mutation in about half of FH patients. These figures compare favourably with best success rates achieved overseas. To date, we have identified and recruited 450 relatives of the 120 index cases in the first 18 months of the pilot program and we expect to increase that number in the future through continued family contact. Cascade screening in 2009 of the first 21 families known to be mutation positive has so far yielded 75 relatives of whom 38 were identified as new FH mutation-positive cases- very close to the 50% theoretically (Hardy-Weinberg) predicted. This pilot program is already providing excellent opportunities for aggressive cardiovascular risk minimisation through dietary and drug strategies coupled with appropriate lifestyle interventions, especially avoidance of smoking and overweight.
Acknowledgements to Frank van Bockxmeer on behalf of Amanda Hooper, Lan Nguyen and John Burnett, Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Western Australia.
Challenges for Society in the Genetic Information Age
OPHG hosted a Challenges for Society in the Genetic Information Age seminar, held on Monday 11 May, 2009. This seminar was intended to raise bioethical and social issues regarding genetics for society. International presenters from the University of British Columbia, Canada and the Indiana University, USA gave talks about possible new directions in bioethics, the social impact of public involvement in genetics and predictive health in the translation of bioethics policy.
GSWA audit
In Western Australia, Genetic Services WA (GSWA) provides a full range of diagnostic and counselling services for individuals at increased risk of familial breast, ovarian and colorectal cancers. Individuals at risk are referred to GSWA through general practitioners or specialists, from other family members who are registry clients or through self-referral when there is a strong family history.
OPHG is currently undertaking an audit of GP and specialist referrals to GSWA for breast/ovarian and colorectal cancers in order to determine the type and accuracy of information provided in the referral, the reason for referral, and if the referral is appropriate. The study has been approved by King Edward Hospital for Women Ethics Committee and all patients’ personal identifying information is removed for the purposes of the audit.
Data has been collated from June to October 2008 and analysis is underway. Findings from this audit will provide evidence as to whether enough information is being collected by GPs and specialists to inform risk stratification for referral to GSWA, reasons for referrals from health professionals and if referrals are appropriate.
Duchenne Muscular Dystrophy National Register
The Clinical, Technical and Ethical Principle Committee of the Australian Health Ministers’ Advisory Council requested OPHG establish and lead a working group to prepare a report and recommendations paper on establishing a National Register for those affected by Duchenne muscular dystrophy (DMD).
DMD is characterised by progressive muscle weakness in all muscle groups including legs, arms, chest and heart resulting in respiratory and cardiac failure leading to early death in the late teens/early 20s. Although this disorder is comparatively uncommon – affecting about 1 in 3,000 people – the impact is enormous, the burden of disease grossly disproportionate to the frequency. Until recently, the most that patients with DMD, and their families, could hope for was to be given a diagnosis and to manage the disease symptoms through physical interventions and community assistance. The explosion of knowledge on the genetic basis and molecular pathophysiology of DMD over the past decade are now being translated into the development of novel therapies that alter the natural history of this previously untreatable disorder.
The purpose of the Register is “To provide Australian families with the opportunity to improve the outcomes of affected individuals”. The potential benefits include enabling coordination of diagnosis, therapy and prevention in an equitable and consistent manner across Australia and for the centralised information to provide an interface between patients, doctors and researchers. It is also hoped that the Register will promote a sense of community and belonging among affected patients and families and provide ready access to information concerning standards of care, research and available therapies.
To this end the DMD working group recently initiated a meeting with stakeholders attending the Genes for Health conference in Perth in May. Stakeholders that attended this meeting included experts in clinical, diagnostic and research areas of Duchenne muscular dystrophy. The stakeholder feedback was very fruitful and the suggestions and observations are currently being drafted into a preliminary set of recommendations for the register. Further stakeholder consultation will take place over the next few months and anyone wishing to provide comments is invited to contact the working group secretariat Leanne Youngs on Leanne.Youngs@health.wa.gov.au.
Publications
In collaboration with other organisations, staff from the OPHG have recently had the following articles published:
Brameld KJ, Dickinson J, O’Leary P, Bower C, Goldblatt J, Hewitt B, Murch A, Stock R. (2008). First Trimester Predictors of Adverse Pregnancy Outcomes. Australian and New Zealand Journal of Obstetrics and Gynecology, 48 (5): 29-535.
Cocciolone R, Brameld KJ, O’Leary P, Haan E. (2008). Combining first and second trimester markers for Down syndrome screening – think twice. Australian and New Zealand Journal of Obstetrics and Gynecology, 48 (5) 492-500.
Maxwell, SJ., Molster, CM., Poke, SJ., & O’Leary, P. (2009). Communicating Familial Hypercholesterolemia genetic information within families. Genetic Testing and Molecular Biomarkers, 13 (3): 301-306.
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