Rare Disease has been identified by the Global Alliance for Genomics and Health as one of two key areas where a collaborative data-sharing approach has the most immediate potential to directly benefit patients.
The Australian Genomics Flagship model is designed to drive our research into nationwide implementation of genomic testing, integrating with our four research programs as frameworks for translation.
Each Flagship project is underpinned by strong existing national and international clinical, diagnostic and research partnerships.
The partnerships are supporting a ‘virtuous cycle’ of rapid translation and implementation through the exchange of information between clinicians and researchers to evaluate pathogenicity, gene discovery and the development of innovative diagnostic and treatment tools.
The Acute Care Genomics study was established in 2018 to implement and evaluate a comprehensive multi-centre network for ultra-rapid genomic diagnosis in the Australian healthcare system.
Ultra-rapid genomic testing (less than 5 day turn-around) is only available at a handful of centres worldwide, and the Acute Care Genomics study is the first to provide rapid testing for rare disease diagnosis at a national level.
In its first phase, the Acute Care Genomics Flagship has provided ultra-rapid genomic testing to more than 200 critically ill babies and children from across 12 Australian hospitals, with results available to most families in just three days.
The study has conducted an initial evaluation of the program, which is available to download here. The paper reports on the diagnostic and clinical outcomes from the first 108 babies and children tested through the study and discusses the system level changes necessary to implement a national ultra-rapid genomic testing program in the Australian context.
In May 2020, the Acute Care Genomics study team were granted $5m in funding from the Australian Government’s Medical Research Future Fund (Genomics Health Futures Mission).
The funding will enable the expansion of the Acute Care Genomics research network to build further capacity in all Australian states and territories, and deliver ultra-rapid testing to more than 240 critically-ill children over the next three years.
This expanded study will allow researchers to fully evaluate whole-genome sequencing as a first tier test for ultra-rapid diagnosis and further prepare the Australian workforce for future mainstreaming.
Read more about the impact of the Acute Care Genomics study in our Personal Stories.
Leads
A/Prof Zornitza Stark (clinical lead)
Australian Genomics and Victorian Clinical Genetics Services
Dr Sebastian Lunke (laboratory lead)
Victorian Clinical Genetics Services
Project Officer
Sophie Bouffler
Australian Genomics
Victoria
Sam Ayres
Victorian Clinical Genetics Services
Dr Stephanie Best
Australian Genomics & Murdoch Children’s Research Institute
Gemma Brett
Victorian Clinical Genetics Services
Dr Belinda Chong
Victorian Clinical Genetics Services
Prof John Christodoulou
Murdoch Children’s Research Institute
Dr Michelle De Silva
Victorian Clinical Genetics Services
Dr Stephanie Eggers
Victorian Clinical Genetics Services
Prof Clara Gaff
Melbourne Genomics Health Alliance
Lyndon Gallacher
Victorian Clinical Genetics Services
Dr Ilias Goranitis
The University of Melbourne
Victoria
Dr Katherine Howell
The Royal Children’s Hospital
Dr Matthew Hunter
Monash Health
Dr Emma Krzesinski
Monash Health
Fiona Lynch
Murdoch Children’s Research Institute
Dr Melissa Martyn
Melbourne Genomics Health Alliance
Belinda McClaren
Murdoch Children’s Research Institute
Dr Amy Niselle
Australian Genomics & Melbourne Genomics
A/Prof Christiane Theda
The Royal Women’s Hospital
Dr Anand Vasudevan
The Royal Women’s Hospital
A/Prof Sue White
Victorian Clinical Genetics Services
New South Wales
Kirsten Boggs
Sydney Children’s Hospital Network
Dr Alessandra Bray
Australian Genomics & Sydney Children’s Hospital Network
A/Prof Michael Buckley
NSW Health Pathology
Dr Lisa Ewans
Royal Prince Alfred Hospital
Ron Fleischer
Royal Prince Alfred Hospital
Dr Himanshu Goel
Hunter Genetics
Prof Edwin Kirk
Sydney Children’s Hospital
Dr David Mowat
Sydney Children’s Hospital
Dr Jason Pinner
Sydney Children’s Hospital
A/Prof Tony Roscioli
Sydney Children’s Hospital
Dr Sarah Sandaradura
The Children’s Hospital at Westmead
A/Prof Meredith Wilson
The Children’s Hospital at Westmead
Queensland
Dr Lindsay Fowles
Genetic Health Queensland
Dr Chirag Patel
Royal Brisbane and Women’s Hospital
Queensland Children’s Hospital
Dr Michael Quinn
Australian Genomics &
Genetic Health Queensland
A/Prof Luregn Schlapbach
Queensland Children’s Hospital
South Australia
A/Prof Chris Barnett
Women’s and Children’s Hospital
Anne Baxendale
Women’s and Children’s Hospital
Sarah Borrie
Women’s and Children’s Hospital
Prof Jozef Gecz
University of Adelaide
Participating clinical sites
- The Royal Children’s Hospital, Melbourne
- Monash Health, Melbourne
- The Royal Women’s Hospital, Melbourne
- The Children’s Hospital at Westmead, Sydney
- Sydney Children’s Hospital Randwick, Sydney
- Westmead Hospital, Sydney
- The Royal Hospital for Women, Sydney
- Hunter Children’s Hospital, Sydney
- Royal Prince Alfred Hospital, Sydney
- Queensland Children’s Hospital, Brisbane
- Royal Brisbane and Women’s Hospital, Brisbane
- Women’s and Children’s Hospital, Adelaide
Participating laboratories
- NSW Health Pathology
- Victorian Clinical Genetics Services
The Acute Care Genomics study (2018-2020) was established with support of The Royal Children’s Hospital Foundation, the Sydney Children’s Hospital Network, the Channel Seven Children’s Research Foundation and Australian Genomics (NHMRC grant 1113531).
Its next phase (2020-2023) has been funded by the Australian Government’s Medical Research Future Fund and it will continue to deliver testing through the infrastructure and support of the Australian Genomics network.
Relevant Publications
Rapid exome sequencing and adjunct RNA studies confirm the pathogenicity of a novel homozygous ASNS splicing variant in a critically ill neonate.
Akesson LS, Bournazos A, Fennell A, Krzesinski EI, Tan K, Springer A, et al. Human mutation. 2020.
Parental experiences of ultra-rapid genomic testing for their critically unwell infants and children.
Brett GR, Martyn M, Lynch F, de Silva MG, Ayres S, Gallacher L, et al. Genetics in medicine : official journal of the American College of Medical Genetics. 2020.
Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System.
Australian Genomics Health Alliance Acute Care Flagship. JAMA. 2020;323(24):2503–2511.
The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.
Riley, L.G., Rudinger-Thirion, J., Frugier, M., Wilson, M., Luig, M., Alahakoon, T.I., et al. (2020). Human Mutation.
Use of ultra-rapid whole-exome sequencing to diagnose congenital central hypoventilation syndrome.
Shanthikumar, S., Kevat, A., Stapleton, R., Lunke, S., Stark, Z., & Vandeleur, M. (2020). Pediatr Pulmonol, 55(4), 855-857.
Rapid Identification of Biallelic SPTB Mutation in a Neonate with Severe Congenital Hemolytic Anemia and Liver Failure.
Richmond, C.M., Campbell, S., Foo, H.W., Lunke, S., Stark, Z., Moody, A., et al. (2020). Mol Syndromol, 11(1), 50-55.
Attitudes of Australian health professionals towards rapid genomic testing in neonatal and paediatric intensive care.
Stark, Z., Nisselle, A., McClaren, B., Lynch, F., Best, S., Long, J.C., et al. (2019). Eur J Hum Genet, 27(10), 1493-1501.
Early diagnosis of Pearson syndrome in neonatal intensive care following rapid mitochondrial genome sequencing in tandem with exome sequencing.
Akesson, L.S., Eggers, S., Love, C.J., Chong, B., Krzesinski, E.I., Brown, N.J., et al. (2019). European Journal of Human Genetics.
IREB2-associated neurodegeneration
Cooper, M.S., Stark, Z., Lunke, S., Zhao, T., & Amor, D.J. (2019). IREB2-associated neurodegeneration. Brain.
Rapid Challenges: Ethics and Genomic Neonatal Intensive Care
Gyngell, C., Newson, A.J., Wilkinson, D., Stark, Z., & Savulescu, J. (2019). Rapid Challenges: Ethics and Genomic Neonatal Intensive Care. Pediatrics, 143(Suppl 1), S14-s21.
Missense variants in TAF1 and developmental phenotypes: challenges of determining pathogenicity.
Cheng, H., Capponi, S., Wakeling, E., Marchi, E., Li, Q., Zhao, M., et al. (2019). Human Mutation.
Genetic counseling in pediatric acute care: Reflections on ultra-rapid genomic diagnoses in neonates.
Ayres, S., Gallacher, L., Stark, Z., & Brett, G.R. (2019). Genetic counseling in pediatric acute care: Reflections on ultra-rapid genomic diagnoses in neonates. J Genet Couns, 28(2), 273-282.
Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function.
Rehman, A.U., Najafi, M., Kambouris, M., Al-Gazali, L., Makrythanasis, P., Rad, A., et al. (2019). Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function. Hum Mutat, 40(3), 267-280.
Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application?
Friedman JM, Bombard Y, Cornel MC, Fernandez CV, Junker AK, Plon SE, et al. 2018. Genetics in Medicine.
View more publications
Despite the relatively common prevalence of inherited cardiovascular disorders, there is no clear or consistent funding mechanism to provide cardiac genetic testing in Australia.
In the Cardiovascular Genetic Disorders Flagship, researchers and doctors are enabling genomic testing for those with genetic heart diseases, including inherited cardiomyopathy (heart muscle diseases), primary arrhythmia (where the heart beats abnormally), and congenital heart disease (where there is a problem with the heart’s structure from birth).
The Flagship is enrolling up to 600 participants from across the country to undergo testing using whole genome sequencing techniques.
By doing so, the Flagship aims to demonstrate the clinical utility and cost effectiveness of genomic testing approaches in genetic heart disease to make the case for standardised and subsidised cardiac genetic testing in Australia.
The Flagship is evaluating the impact on families following the genetic diagnosis of a family member, so as to inform screening and additional testing for family members (called ‘cascade testing’). The Flagship has a considerable research component embedded in its design, bringing together expert cardiac researchers across the nation and working towards the establishment of an Australia-wide database of genetic variants found in enrolled patients to support collaborative diagnosis and further research.
In tandem with genomic testing, the Flagship is undertaking several projects designed to evaluate current standards of care for those with genetic heart disease:
- Investigating the current models of care for genetic heart disease families in Australia: a nation-wide clinical cardiac audit that seeks to determine what the current models of care are for cardiac genetic testing referrals in Australia, and to identify clinic-to-clinic differences.
- Evaluating genetic testing and counselling for congenital heart disease. This project is surveying adult and paediatric clinicians to investigate the significant differences in referral rates to cardiac genetic testing for patients with congenital heart disease.
- Determining the effectiveness of genomic sequencing study. This study aims to evaluate the effects of genetic testing on the clinical management of patients with genetic heart diseases through identifying what the effects of genomic sequencing are on clinical diagnosis, medications, frequency of cardiology visits and family screening recommendations.
Together with enabling whole genome sequencing for enrolled participants, and collecting data across the broad range of studies described above, the Cardiovascular Genetic Disorders Flagship is collecting evidence to develop a unified “best practice” approach to cardiac genetic testing. The evidence collected will be used to inform policy, to educate the clinical workforce, and to help prepare Australia for the use of genomic medicine in the clinical care of those with genetic heart diseases.
Leads
Prof Chris Semsarian
The University of Sydney & Centenary Institute
A/Prof Julie McGaughran
Genetic Health Queensland
Coordinators
Jaye Brown
Centenary Institute
Rachel Austin
Genetic Health Queensland
Clinical sites and state leads
Dr Jodie Ingles
Centenary Institute
Prof Edwin Kirk
Sydney Children’s Hospital
Prof Diane Fatkin
Victor Chang Cardiac Research Institute
Prof Richard Harvey
Victor Chang Cardiac Research Institute
Prof David Winlaw
The Children’s Hospital at Westmead
Prof Sally Dunwoodie
Victor Chang Cardiac Research Institute
Dr Gillian Blue
The Children’s Hospital at Westmead
A/Prof Robert Weintraub
The Royal Children’s Hospital
Clinical sites and state leads
A/Prof Paul James
Murdoch Children’s Research Institute
Prof Jitu Vohra
The Royal Melbourne Hospital
A/Prof John Atherton
Royal Brisbane Women’s Hospital
Dr James Morwood
Lady Cilento Children’s Hospital
Prof Eric Haan
SA Pathology at Royal Adelaide Hospital
A/Prof Chris Barnett
Women’s and Children’s Hospital
Dr Andrew Kelly
Women’s and Children Hospital
A/Prof Nicholas Pachter
Genetic Services of Western Australia, King Edward Memorial Hospital
Working Group
Dr Andrew Davis
The Royal Children’s Hospital
Prof Paul Scuffham
Centre for Applied Health Economics, Griffith University
Dr Kelly Smith
The University of Queensland
A/Prof Ben Hogan
The University of Queensland
Dr Alejandro Metke
CSIRO
Dr Alison Colley
Liverpool Hospital
Angela Ingrey
Hunter Genetics
Angela Overkov
King Edward Memorial Hospital
Anne Ronan
Hunter Genetics
Elle Martin
The Children’s Hospital at Westmead
Dr Karin Van Spaendonck-Zwarts
Genetic Health Queensland
Dr Kathryn Waddell-Smith
Flinders Medical Centre
Kathy Cox
SA Pathology
Lesley Ades
The Children’s Hospital at Westmead
Working Group
A/Prof Enzo Porello
Murdoch Children’s Research Institute
Dr Richard Bagnall
Centenary Institute
Dr Raymond Sy
Royal Prince Alfred Hospital
Dr Janet George
Cardiomyopathy Association of Australia
Prof Jamie Vandenberg
Victor Chang Cardiac Research Institute
Dr Sebastian Lunke
Victorian Clinical Genetics Services
Dr Michael Cheung
The Royal Children’s Hospital
Dr Bernadette Hanna
Westmead Hospital
Dr David Elliot
Murdoch Children’s Research Institute
A/Prof Dominica Zentner
The Royal Melbourne Hospital
Linda Wornham
Genetic Health Queensland
A/Prof Meredith Wilson
The Children’s Hospital at Westmead
Dr Michelle de Silva
Victorian Clinical Genetics Services & Australian Genomics
Dr Nicole Schonrock
Genome.One
Working Group
Eddy Kizana
Westmead Hospital
Dr Eleni Giannoulatou
Victor Change Cardiac Research Institute
Gemma Correnti
SA Clinical Genetics Service
Georgina Hollway
QIMR Berghofer Medical Research Institute
Dr Igor Konstantinov
The Royal Children’s Hospital
Ivan Macciocca
Victorian Clinical Genetics Services
James Chong
Westmead Hospital
Dr James Hudson
QIMR Berghofer Medical Research Institute
Janine Smith
The Children’s Hospital at Westmead
Dr Karen Carpenter
PathWest
Paula Murray
Heart Kids
Dr Sarah Kummerfeld
Garvan Institute of Medical Research
Dr Sulekah Rajagopalan
Liverpool Hospital
Tina Thompson
Royal Melbourne Hospital
- Hunter Genetics
- Royal Prince Alfred Hospital
- Liverpool Hospital
- St Vincent’s Hospital Sydney
- Sydney Children’s Hospital Randwick
- The Children’s Hospital at Westmead
- Westmead Hospital
- Queensland Children’s Hospital
- Royal Brisbane and Women’s Hospital
- The Royal Children’s Hospital
- The Royal Melbourne Hospital
- Women’s and Children’s Hospital
- Royal Adelaide Hospital
- King Edward Memorial Hospital
- Royal Perth Hospital
- Australian Government’s Medical Research Future Fund
- Australian Genomics
- Australian Genetic Heart Disease Registry
- Australian Cardiac Genetic Testing (ACTG)
- Heart Kids
- Cardiomyopathy Association of Australia
Relevant Publications
Current Practice of Genetic Testing and Counselling in Congenital Heart Disease: An Australian Perspective.
Blue GM, Smith J, Sholler GF, Semsarian C, Winlaw DS, Australian Genomics Cardiovascular Genetic Disorders Flagship. Heart, lung & circulation. 2020.
Interstitial and Diffuse Lung Disease describes a diverse group of rare chronic lung disorders in children, most common in early infancy.
The lung and surrounding tissue that provides the support structure of the lung’s air sacs, (the alveoli) to transfer oxygen into the blood stream becomes inflamed and stiff affecting oxygen delivery. The term “chILD” has been adopted internationally to describe all these disorders.
Diagnosing these disorders is difficult because the signs and symptoms can be broad. Although genomic technologies have enabled the discovery of new genes relating to chILD, there is no standard approach to diagnosing the disorders, nor reviewing undiagnosed cases in light of these gene discoveries.
‘chILDRANZ’ is an Australian & New Zealand network of doctors and researchers collaborating across the globe to improve healthcare for children affected by these lung disorders.
The Australian Genomics chILDRANZ Flagship (Interstitial and Diffuse Lung Disease in Children) is enrolling children from across every state and territory in Australia to build evidence to improve standards of care, genomic testing and referral practices; increasing the diagnostic awareness of chILD; standardising management of the diseases, and offering the opportunity to participate in the first international clinical trial in chILD currently underway in Europe.
The Lung Foundation Australia and the Young Lungs Parent Advisory Group are also key collaborators in the chILDRANZ Flagship.
Lead
Prof Adam Jaffe
University of New South Wales & Sydney Children’s Hospital
Flagship Coordinator
Nada Mirkovic
Australian Genomics & University of New South Wales
Advisors
Prof Phillip Clarke
The University of Melbourne
Prof Kei Lui
Australia and New Zealand Neonatal Intensive Care Network lead
Dr Marian Festa
Australia and New Zealand Paediatric Intensive Care Network
Working group
Dr André Schultz
Perth Children’s Hospital
Dr David Mowat
Sydney Children’s Hospital
Dr Suzanna Lindsey-Temple
Sydney Children’s Hospital
A/Prof Bruce Bennetts
The Sydney Children’s Hospital at Westmead
Ms Gladys Ho
The Sydney Children’s Hospital at Westmead
Dr Melanie Wong
The Sydney Children’s Hospital at Westmead
Prof John Christodoulou
Murdoch Children’s Research Institute
Dr Vishal Saddi
Sydney Children’s Hospital
Working Group
Ms Kirsten Boggs
Australian Genomics
Ms Liz Vuletich
Young Lungs Parent Advisory group, Lung Foundation Australia
Ms Tania Prior Smith
Young Lungs Parent Advisory group, Lung Foundation Australia
Mr Mark Brooke
CEO, Lung Foundation Australia
Ms Kelcie Herrmann
Lung Foundation Australia
Ms Jane Kerr
Lung Foundation Australia
Ms Jamie Maloney
Lung Foundation Australia
Clinical site leads
Victoria
Dr Joanne Harrison
The Royal Children’s Hospital
The Royal Women’s Hospital
Monash Health
South Australia
Dr Andrew Tai
Women’s and Children’s Hospital
Western Australia
Dr André Schultz
Perth Children’s Hospital
King Edward Memorial Hospital
Queensland
A/Prof Nitin Kapur
Queensland Children’s Hospital
Royal Brisbane and Women’s Hospital
Tasmania
Dr Sean Beggs
Royal Hobart Hospital
New South Wales & The ACT
Prof Adam Jaffe
The Royal Hospital for Women
Sydney Children’s Hospital, Randwick
Dr Lisa Ewans
Royal Prince Alfred Hospital
Prof Joerg Mattes
John Hunter Children’s Hospital
Dr Jaqueline Stacks
Liverpool Hospital
A/Prof Hiran Selvadurai
The Children’s Hospital at Westmead
Dr Tim Macdonald
The Canberra Hospital
- The Canberra Hospital
- John Hunter Children’s Hospital
- Westmead Hospital
- Liverpool Hospital
- Royal Prince Alfred
- The Royal Hospital for Women
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- Queensland Children’s Hospital
- Royal Brisbane and Women’s Hospital
- Women’s and Children’s Hospital
- The Royal Children’s Hospital
- Royal North Shore Hospital
- Royal Hobart Hospital
- Royal Children’s Hospital
- Royal Women’s Hospital
- Monash Health
- King Edward Memorial Hospital
- Perth Children’s Hospital
- Australian Genomics
- Lung Foundation Australia
- Young Lungs Parent Advisory Group
- The ChILDRANZ network
- Thoracic Society of Australia and New Zealand (TSANZ)
- chILD- EU
- US chILD Research Network
Relevant Publications
Children’s interstitial and diffuse lung disease
Cunningham, S., Jaffe, A., & Young, L.R. (2019). Children’s interstitial and diffuse lung disease. Lancet Child Adolesc Health, 3(8), 568-577.
The European research collaboration for Children’s Interstitial Lung Disease (ChILDEU) ERS Clinical Research Collaboration.
Cunningham, S., Gilbert, C., & Schwerk, N. (2018). The European research collaboration for Children’s Interstitial Lung Disease (ChILDEU) ERS Clinical Research Collaboration. Eur Respir J, 52(6).
Childhood interstitial lung diseases in immunocompetent children in Australia and New Zealand: a decade’s experience
Saddi, V., Beggs, S., Bennetts, B., Harrison, J., Hime, N., Kapur, N., et al. (2017). Childhood interstitial lung diseases in immunocompetent children in Australia and New Zealand: a decade’s experience. Orphanet J Rare Dis, 12(1), 133.
Childhood interstitial lung disease: A systematic review.
Hime, N.J., Zurynski, Y., Fitzgerald, D., Selvadurai, H., Phu, A., Deverell, M., et al. (2015). Childhood interstitial lung disease: A systematic review. Pediatr Pulmonol, 50(12), 1383-1392.
wHole genome Investigation to iDentify unDEtected Nephropathies – Applying Genomics to Understand Unexplained End Stage Kidney Disease
End Stage Kidney Disease (ESKD) is a disease stage where a person’s kidneys no longer function sufficiently and potential treatment with life-sustaining renal replacement therapies such as dialysis or a kidney transplant are indicated.
ESKD of ‘unknown cause’ describes those without a definitive diagnosis for their kidney disease, despite an overwhelming excess burden of morbidity and mortality that these patients experience. For many, the traditional diagnostic avenues have been exhausted in an attempt to reveal the cause of the disease. This ‘diagnostic odyssey’ and also therapeutic odyssey experienced has an enormous impact on these individuals and families.
The KidGen Collaborative ‘HIDDEN’ Flagship is investigating whether genomic sequencing can help to diagnose and better guide clinical management of patients with ESKD. The Flagship is enrolling participants with ESKD and no definitive diagnosis, so as to establish evidence for new approaches that may result in answers for patients, their families and the broader community. The Flagship will also evaluate the role of dynamic consent, health economics, and pharmacogenomics in bringing further benefit to the ESKD population beyond a diagnostic evaluation.
The KidGen Collaborative HIDDEN Flagship is internationally networked, and collaborates closely with Kidney Health Australia.
Follow KidGen on Twitter to hear more about their progress @kidgenaustralia
Leads
A/Prof Andrew Mallett
Royal Brisbane and Women’s Hospital
Dr Cathy Quinlan
The Royal Children’s Hospital
Dr Amali Mallawaarachchi
Royal Prince Alfred Hospital
Garvan Institute of Medical Research
Dr Cas Simons
Murdoch Children’s Research Institute
A/Prof Zornitza Stark
Australian Genomics & Victorian Clinical Genetics Services
Dr Chirag Patel
Royal Brisbane & Women’s Hospital & Queensland Children’s Hospital
Program Manager
Louise Wardrop
Australian Genomics & Murdoch Children’s Research Institute
Program Coordinator
Dr Lindsay Fowles
Australian Genomics & Genetic Health Queensland
State Clinical Leads
Queensland
Dr Chirag Patel
Royal Brisbane and Women’s Hospital
Queensland Children’s Hospital
Genetic Counsellor
Dr Lindsay Fowles
New South Wales
Dr Amali Mallawaarachchi
Royal Prince Alfred Hospital
Garvan Institute of Medical Research
Genetic Counsellor
Jayamala Parmar
South Australia
Prof Randall Faull
Royal Adelaide Hospital
Genetic Counsellor
Vanessa Huntley
Western Australia
A/Prof Aron Chakera
Sir Charles Gairdner Hospital
Genetic Counsellor
Mandi MacShane
Northern Territory
Dr Madhivanan Sundaram
Royal Darwin Hospital
Victoria
A/Prof Zornitza Stark
Australian Genomics & Victorian Clinical Genetics Services
Dr Cathy Quinlan
The Royal Children’s Hospital
Genetic Counsellor
Ella Wilkins
Tasmania
Professor Matthew Jose
Royal Hobart Hospital
Genetic Counsellor
Jo Burke
- Royal Brisbane and Women’s Hospital
- Queensland Children’s Hospital
- Royal Prince Alfred Hospital
- Westmead Hospital
- The Children’s Hospital at Westmead
- Sydney Children’s Hospital, Randwick
- The Royal Children’s Hospital
- Royal Melbourne Hospital
- Austin Hospital
- Monash Medical Centre
- Monash Children’s Hospital
- Royal Adelaide Hospital
- Sir Charles Gairdner Hospital
- Perth Children’s Hospital
- Royal Darwin Hospital
- Royal Hobart Hospital
- Australian Genomics
- KidGen Collaborative
- Kidney Health Australia
- Genomics England
- Aotearoa Renal Genetics Study
- The Royal Children’s Hospital Foundation
- Royal Brisbane and Women’s Hospital Foundation
- The University of Queensland
- Royal Prince Alfred Hospital
- Metro North Hospital and Health Service
Relevant Publications
Meeting report of the 2017 KidGen Renal Genetics Symposium
Jayasinghe K, Quinlan C, Stark Z, Patel C, Sampson MG, Saleem M, Mallett AJ and KidGen Collaborative. Meeting report of the 2017 KidGen Renal Genetics Symposium. Human Genomics. 2018. 12 (1) : 5.
Renal genetics in Australia: Kidney medicine in the genomic age.
Jayasinghe, K., Quinlan, C., Stark, Z., Patel, C., Mallawaarachchi, A., Wardrop, L., et al. (2019). Renal genetics in Australia: Kidney medicine in the genomic age. Nephrology (Carlton), 24(3), 279-286.
Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.
Mallett, A.J., McCarthy, H.J., Ho, G., Holman, K., Farnsworth, E., Patel, C., et al. (2017). Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders. Kidney Int, 92(6), 1493-1506.
A multidisciplinary renal genetics clinic improves patient diagnosis.
Mallett, A., Fowles, L.F., McGaughran, J., Healy, H., & Patel, C. (2016). A multidisciplinary renal genetics clinic improves patient diagnosis. Med J Aust, 204(2), 58-59.
Muscular dystrophies comprise over 460 known disease genes, which our research team has studied using panel and whole exome approaches in a clinical context.
The neuromuscular clinical and diagnostic network across Australia is relatively mature, building upon large programs of work including an National Health and Medical Research Council funded Centre of Research Excellence and the Australasian Neuromuscular Network. This project is building upon this network to map current diagnostic practice and study the diagnostic yield from single gene testing as standard of care, targeted panel analysis and whole genome sequencing and RNA-sequencing where appropriate.
The Flagship completed enrolment at the end of December 2018 and is now evaluating the results of this study.
Lead
Prof Nigel Laing
The University of Western Australia and Harry Perkins Institute of Medical Research
Working Group
A/Prof Chris Barnett
South Australian Clinical Genetics Service
Dr Anita Cairns
Children’s Health Queensland
A/Prof Sandra Cooper
Children’s Hospital at Westmead
Dr Mark Davis
PathWest
Dr Roula Ghaoui
Royal Adelaide Hospital
A/Prof Kristi Jones
Sydney Children’s Hospital Network
Prof Phillipa Lamont
Royal Perth Hospital
Dr Suzanna MacLennon
Women’s and Children’s Hospital, Adelaide
Dr David Mowat
Sydney Children’s Hospital Network
A/Prof Kristen Nowak
Harry Perkins Institute of Medical Research
A/Prof Gina Ravenscroft
Harry Perkins Institute of Medical Research
Prof Monique Ryan
The Royal Children’s Hospital
Project Officer
Denise Howting
Harry Perkins Institute of Medical Research
The Neuromuscular Diseases Flagship has completed enrolment and is now evaluating the results of its study. Thank you to the clinicians involved and the following participating clinical sites:
- Austin Health
- Perth Children’s Hospital
- Queensland Children’s Hospital
- Royal Adelaide Hospital
- Royal Hobart Hospital
- Royal Perth Hospital
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- The Royal Children’s Hospital
- Women’s and Children’s Hospital
- Australian Genomics
- PathWest Laboratory Medicine, Department of Health Western Australia
- Royal Perth Hospital Neurogenetics Unit
- The Kids Neuroscience Centre, The Children’s Hospital at Westmead, Sydney
- Australian National Health and Medical Research Council Fellowships and project grants for triaging patients not diagnosed by standard diagnostic practice or the Flagship into further research projects.
Relevant Publications
Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases.
Schofield, D., Alam, K., Douglas, L., Shrestha, R., MacArthur, D.G., Davis, M., et al. (2017). Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases. npj Genomic Medicine, 2(1), 4.
Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.
Cummings, B. B., J. L. Marshall, T. Tukiainen, M. Lek, S. Donkervoort, A. R. Foley, V. Bolduc, L. B., et al, (2017). “Improving genetic diagnosis in Mendelian disease with transcriptome sequencing.” Sci Transl Med 9(386).
“STRetch: detecting and discovering pathogenic short tandem repeat expansions.
Dashnow, H., M. Lek, B. Phipson, A. Halman, S. Sadedin, A. Lonsdale, M. Davis, P. Lamont, J. S. Clayton, N. G. Laing, D. G. MacArthur and A. Oshlack (2018). “STRetch: detecting and discovering pathogenic short tandem repeat expansions.” Genome Biol 19(1): 121.
Mitochondrial diseases are the most common inherited metabolic diseases, affecting more than one in 5000 births and comprising over 200 disease genes that account for over 60% of paediatric cases.
The current diagnostic pathway is not standardised, varying between clinical presentations, from state-to-state, and even from one subspecialty service to another.
This project is comparing current diagnostic approaches of genetic testing or targeted panels with earlier introduction of genomic techniques – Whole Exome Sequencing (WES), mitochondrial DNA sequencing or Whole Genome Sequencing (WGS).
Leads
Prof John Christodoulou
Murdoch Children’s Research Institute
Prof David Thorburn
Murdoch Children’s Research Institute
Coordination support
Dotti Tang
Australian Genomics
Clinical leads - Victoria
Dr Joy Lee
Paediatrics
The Royal Children’s Hospital
Prof Martin Delayticki
Adults
Victorian Clinical Genetics Services
Dr Maie Walsh
The Royal Melbourne Hospital
Prof Michael Fahey
The Royal Melbourne Hospital
Genetic Counsellor
Michelle de Silva
Australian Genomics & Victorian Clinical Genetics Services
Dr Adrienne Sexton
The Royal Melbourne Hospital
Clinical Leads - South Australia
Dr Nick Smith
Paediatrics
Women’s and Children’s Hospital
Dr Janice Fletcher
Adults
SA Pathology
Dr Roula Ghaoui
Royal Adelaide Hospital
Genetic Counsellor
Sarah Borrie
Women’s and Children’s Hospital
Clinical leads - Western Australia
Dr Maina Kava
Paediatrics
Perth Children’s Hospital
Prof Phillipa Lamont
Adults
Royal Perth Hospital
Genetic Counsellor
Mandi McShane
Genetic Services of WA
Clinical leads - Queensland
Prof David Coman
Paediatrics and adult
Lady Cilento Children’s Hospital
Genetic Counsellor
Melanie Tom
Genetic Health Queensland
Clinical leads - New South Wales
Dr Shanti Balasubramaniam
Paediatrics
Sydney Children’s Hospital Network
Dr Michel Tchan
Adults
Westmead Hospital
Genetic Counsellor
Shona Reid
Sydney Children’s Hospital Network
Working group
Prof Mike Ryan
Monash University
Prof Alexandra Filipovska
The University of Western Australia
Dr Carolyn Bursle
The Royal Children’s Hospital
Dr Jo Burke
The Royal Hobart Hospital
Dr Himanshu Goel
Hunter Genetics
Dr Tracy Dudding-Byth
Hunter Genetics
Dr Tyson Ware
The Royal Hobart Hospital
- Hunter Genetics
- Monash Health
- Perth Children’s Hospital
- Queensland Children’s Hospital
- Royal Adelaide Hospital
- Royal Melbourne Hospital
- Royal Perth Hospital
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- The Royal Children’s Hospital
- Westmead Hospital
- Women’s and Children’s Hospital
- Australian Genomics
- Mito Foundation
Australian Genomics gratefully acknowledges the generous funding support of the Mito Foundation toward the sequencing of participants in this Flagship. The Foundation provides funding for research into mitochondrial diseases, delivers support to individuals & families, and provides education on mitochondrial diseases to the public and medical profession.
Clinical Spectrum and Functional Consequences Associated with Bi-Allelic Pathogenic PNPT1 Variants.
Rius, R., Van Bergen, N.J., Compton, A.G., Riley, L.G., Kava, M.P., Balasubramaniam, S., et al. (2019). J Clin Med, 8(11).
Early diagnosis of Pearson syndrome in neonatal intensive care following rapid mitochondrial genome sequencing in tandem with exome sequencing.
Akesson, L.S., Eggers, S., Love, C.J., Chong, B., Krzesinski, E.I., Brown, N.J., et al. (2019). European Journal of Human Genetics.
KidGen is a Queensland-based national research consortium made up of clinicians, counsellors, scientists and researchers working to better understand inherited kidney diseases. The aim is to identify the cause and help provide definitive diagnoses for patients and families. Kidney disease is an important public health issue as it affects around 1 in 8 Australian adults. It is thought that up to 20% have an inherited form of the disease.
The Australian Genomics Renal Genetics Flagship project has built on the KidGen consortium to integrate genomic medicine into care for those with inherited kidney diseases, with the aim to better diagnose, manage and treat these diseases.
The KidGen Collaborative in 2019 has well-established multidisciplinary clinics located every state of Australia and the Northern Territory, through which it is establishing novel diagnostic pathways for genetic and inherited kidney diseases, and to provide a research-genomics arm to undertake functional analysis for those where a diagnosis remains elusive.
The advanced genomics program involves research exome and genome sequencing, providing additional segregation capacity and a more complete genomic analysis. Disease modelling is also undertaken using mouse and kidney organoid model systems, including patient-derived cell lines.
The Flagship completed primary enrolment to its study in 2018. The Flagship and is now analysing data to identify candidates for further investigation to learn more about kidney disease. With further analysis, the aim is to optimise clinical pathways and outcomes for patients with inherited kidney disease.
Lead
A/Prof Andrew Mallett
Royal Brisbane and Women’s Hospital & The University of Queensland
Program Manager
Louise Wardrop
Australian Genomics & Murdoch Children’s Research Institute
Program Coordinator
Dr Lindsay Fowles
Australian Genomics & Genetic Health Queensland
State Clinical Leads
Queensland
Dr Chirag Patel
Royal Brisbane and Women’s Hospital & Queensland Children’s Hospital
Genetic Counsellor
Dr Lindsay Fowles
New South Wales
Dr Amali Mallawaarachchi
Royal Prince Alfred Hospital
Genetic Counsellor
Jayamala Parmar
South Australia
Prof Randall Faull
Royal Adelaide Hospital
Genetic Counsellor
Vanessa Huntley
Western Australia
A/Prof Aron Chakera
Sir Charles Gairdner Hospital
Genetic Counsellor
Mandi MacShane
Northern Territory
Dr Madhivanan Sundaram
Royal Darwin Hospital
Tasmania
Professor Matthew Jose
Royal Hobart Hospital
Genetic Counsellor
Jo Burke
Victoria
A/Prof Zornitza Stark
Australian Genomics & Victorian Clinical Genetics Services
Dr Cathy Quinlan
The Royal Children’s Hospital
Genetic Counsellor
Ella Wilkins
The KidGen Renal Genetics Flagship has now completed enrolment and is now evaluating the results of the study.
Thank you to the clinicians involved and the following participating clinical sites:
- Royal Brisbane and Women’s
- Queensland Children’s Hospital
- Royal Prince Alfred Hospital
- Westmead Hospital
- The Children’s Hospital at Westmead
- Sydney Children’s Hospital, Randwick
- Royal Children’s Hospital
- Royal Melbourne Hospital
- Austin Hospital
- Monash Medical Centre
- Monash Children’s Hospital
- Royal Adelaide Hospital
- Sir Charles Gairdner Hospital
- Perth Children’s Hospital
- Royal Darwin Hospital
- Royal Hobart Hospital
- Australian Genomics
- Melbourne Genomics Health Alliance
- KidGen Collaborative
- Kidney Health Australia
- PKD Australia
- Genomics England
- CPGR (H3ABioNet)
- The Royal Children’s Hospital Foundation
- Royal Brisbane and Women’s Hospital Foundation
- The University of Queensland
- Murdoch Children’s Research Institute
Relevant Publications
Clinical impact of genomic testing in patients with suspected monogenic kidney disease.
Jayasinghe K, Stark Z, Kerr PG, Gaff C, Martyn M, Whitlam J, et al. Genetics in medicine : official journal of the American College of Medical Genetics. 2020.
Isolated proteinuria due to CUBN homozygous mutation – challenging the investigative paradigm.
Jayasinghe, K., White, S.M., Kerr, P.G., MacGregor, D., Stark, Z., Wilkins, E., et al. (2019). BMC Nephrol, 20(1), 330.
Comprehensive evaluation of a prospective Australian patient cohort with suspected genetic kidney disease undergoing clinical genomic testing: a study protocol.
Jayasinghe, K., Stark, Z., Patel, C., Mallawaarachchi, A., McCarthy, H., Faull, R., et al. (2019). BMJ Open.
Meeting report of the 2017 KidGen Renal Genetics Symposium
Jayasinghe K, Quinlan C, Stark Z, Patel C, Sampson MG, Saleem M, Mallett AJ and KidGen Collaborative. Meeting report of the 2017 KidGen Renal Genetics Symposium. Human Genomics. 2018. 12 (1) : 5.
Renal genetics in Australia: Kidney medicine in the genomic age.
Jayasinghe, K., Quinlan, C., Stark, Z., Patel, C., Mallawaarachchi, A., Wardrop, L., et al. (2019). Renal genetics in Australia: Kidney medicine in the genomic age. Nephrology (Carlton), 24(3), 279-286.
Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.
Mallett, A.J., McCarthy, H.J., Ho, G., Holman, K., Farnsworth, E., Patel, C., et al. (2017). Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders. Kidney Int, 92(6), 1493-1506.
A multidisciplinary renal genetics clinic improves patient diagnosis.
Mallett, A., Fowles, L.F., McGaughran, J., Healy, H., & Patel, C. (2016). A multidisciplinary renal genetics clinic improves patient diagnosis. Med J Aust, 204(2), 58-59.
The Neurodevelopmental Disability Flagship is an amalgamation of clinical areas with some overlapping features and recruitment pathways.
The studies within this Flagship are:
-
Epileptic Encephalopathies
-
Brain Malformations
-
Leukodystrophies
-
Intellectual Disabilities
Current diagnostic practice for these disorders varies from state-to-state, so these Flagships are mapping and evaluating the existing clinical pathways, and evaluating the feasibility and utility of genomic testing approaches for children with epileptic encephalopathies, leukodystrophies and intellectual disabilities.
It is hoped that genomic diagnosis early in the diagnostic journey will reduce some invasive diagnostic tests, and better direct clinical care including optimising the choice of therapy in patients.
The Brain Malformations and Epileptic Encephalopathies studies have now completed enrolment of participants and are evaluating the outcomes of these studies.
Lead - Neurodevelopmental Disability Flagship
Prof Jozef Gecz
University of Adelaide
Brain Malformations and Leukodystrophy Flagship Leads
A/Prof Rick Leventer
The Royal Children’s Hospital
A/Prof Paul Lockhart
Murdoch Children’s Research Institute
Brain Malformations and Leukodystrophy state leads
Dr Kate Riney
Children’s Health Queensland
Dr Chris Barnett
SA Clinical Genetics Services
Dr John Silberstein
Princess Margaret Hospital
Brain Malformations and Leukodystrophy state leads
Dr Rani Sachdev
Sydney Children’s Hospital, Randwick
Dr Shekeeb Mohammad
The Children’s Hospital at Westmead
Dr Cas Simons (Research)
Murdoch Children’s Research Institute
Epileptic Encephalopathy Flagship Lead
Prof Ingrid Scheffer
The University of Melbourne
Epileptic Encephalopathy state leads
Dr Deepak Gill
The Children’s Hospital at Westmead
Dr Katherine Howell
The Royal Children’s Hospital
Dr Steve Malone
Queensland Children’s Hospital
Epileptic Encephalopathy state leads
Prof Lakshmi Nagarajan
Perth Children’s Hospital
Dr Clair Pridmore
SA Health
Dr Tyson Ware
Royal Hobart Hospital
Intellectual Disability Flagship Leads
A/Prof Tony Roscioli
Sydney Children’s Hospital, Randwick
Prof Mike Field
GoLD / Hunter Genetics
Intellectual Disabilities
- Hunter Genetics
- King Edward Memorial Hospital
- Liverpool Hospital
- Royal Prince Alfred Hospital
- Royal Brisbane and Women’s Hospital
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- The Royal Children’s Hospital
- Women’s and Children’s Hospital
Leukodystrophies
- Austin Health
- Monash Medical Centre
- Perth Children’s Hospital
- Queensland Children’s Hospital
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- The Royal Hobart Hospital
- The Royal Children’s Hospital
- Women’s and Children’s Hospital
The Brain Malformations and Epileptic Encephalopathies studies have now completed enrolment of participants and are evaluating the outcomes of these studies.
Thank you to all the clinicians from the following participating clinical sites:
Brain Malformations
- Austin Health
- Monash Medical Centre
- Perth Children’s Hospital
- Queensland Children’s Hospital
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- The Royal Hobart Hospital
- The Royal Children’s Hospital
- Women’s and Children’s Hospital
Epileptic Encephalopathies
- Austin Health
- Monash Medical Centre
- Perth Children’s Hospital
- Queensland Children’s Hospital
- Sydney Children’s Hospital
- The Children’s Hospital at Westmead
- The Royal Hobart Hospital
- The Royal Children’s Hospital
- Women’s and Children’s Hospital
- Australian Genomics
- Leukodystrophy Australia
- Mission Massimo Foundation
Relevant publications
Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy
Perucca, P, Scheffer IE, Harvey S, James P, Lunke S, Thorne N, et al. Real-world utility of whole exome sequencing with targeted gene analysis for focal epilepsy. Epilepsy Research. 2017. 131 : 1—8.
Parental Mosaicism in “De Novo” Epileptic Encephalopathies
Myers CT, Hollingsworth G, Muir AM, Schneider AL, Thuesmunn Z, Knupp A, et al. Parental Mosaicism in “De Novo” Epileptic Encephalopathies. New England Journal of Medicine. 2018. 378 (17) : 1646-1648.
Genomic diagnosis for children with intellectual disability and/or developmental delay
Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, et al. Genomic diagnosis for children with intellectual disability and/or developmental delay. Genome Medicine. 2017. 9 (1<) : 43.
Genetic immune disorders comprise over 300 monogenic disorders plus a range of complex multigenic disorders.
The Genetic Immunology Flagship is focusing on early-onset conditions such as Severe Combined Immunodeficiency and Early Onset Autoinflammatory or Autoimmune Diseases, where monogenic causes can be identified in more than 70% of cases.
There is an unmet need for genetic diagnosis of immunological diseases, which is likely to be at least partially resolved by genomics, particularly whole exome or whole genome sequencing.
The Immunology Flagship represents two key deliverables of Australian Genomics: firstly, that considerable benefit will flow from obtaining early genetic diagnoses for patients with primary immune deficiencies, early onset autoimmunity and auto inflammatory diseases.
Secondly, that established research programs will enhance our chances of resolving cases in which known diseases-associated mutations are not identified.
The Flagship study provides an opportunity for transforming our diagnostic approach to patients with these diseases; we expect that greater case ascertainment, together with a national collaborative effort, should also build capacity for research in immunological diseases.
Lead
Prof Matthew Cook
The Australian National University
Flagship Coordinator
Bryony Curran
The Australian National University
State leads - Victoria
Dr Vanessa Bryant
Walter and Eliza Hall Institute of Medical Research
Dr Sharon Choo
The Royal Children’s Hospital
Dr Seth Masters
Walter and Eliza Hall Institute of Medical Research
Dr Fiona Moghaddas
Walter and Eliza Hall Institute of Medical Research
State leads - New South Wales & ACT
Dr Melanie Wong
The Children’s Hospital at Westmead
Prof Carola Vinuesa
The Australian National University
State leads - Western Australia
Dr Andrew McLean-Tooke
Sir Charles Gairdner Hospital
Working Group
Prof Stephen Alexander
The Children’s Hospital at Westmead
Dr Dan Andrews
The Australian National University
Dr Tatjana Banovic
Royal Adelaide Hospital
Dr Ed Bertram
The Australian National University
Prof Matthew Brown
Queensland University of Technology
Dr Theresa Cole
The Royal Children’s Hospital
Prof Jo Douglass
Melbourne Health
Dr Paul Gray
Sydney Children’s Hospital
A/Prof Shane Grey
Garvan Institute of Medical Research
A/Prof Jane Peake
Queensland Children’s Hospital
Prof Richard Kitching
Monash University
Prof Fabienne MacKay
The University of Melbourne
Dr Charlotte Slade
Melbourne Health
Dr Joanne Smart
The Royal Children’s Hospital
Prof Stuart Tangye
Garvan Institute of Medical Research
Dr Phil Wu
The Australian National University
Dr Stephanie Richards
The Royal Children’s Hospital
Dr Lloyd D’Orsogna
Fiona Stanley Hospital
Dr Elina Tan
Royal Perth Hospital
Dr Julian Bosco
The Alfred
A/Prof Menno van Zelm
Monash University
Prof Michael Gold
Women’s and Children’s Hospital
Dr Patrick Quinn
Women’s and Children’s Hospital
Dr Pravin Hissaria
Royal Adelaide Hospital
Dr Samar Ojaimi
Monash Health
Ms Stephanie Badman
The Canberra Hospital
- Austin Health
- Fiona Stanley
- Liverpool Hospital
- Monash Health
- Monash Medical Centre
- Perth Children’s Hospital
- Queensland Children’s Hospital
- Royal Adelaide Hospital
- Royal Melbourne Hospital
- Royal Perth Hospital
- Royal Prince Alfred
- Sir Charles Gairdner Hospital
- Sydney Children’s Hospital Randwick
- The Alfred
- The Canberra Hospital
- The Children’s Hospital at Westmead
- The Royal Children’s Hospital
- Women’s and Children’s Hospital
- Australian Genomics
- Canberra Clinical Genomics
- Centre for Personalised Immunology
- Australian Autoinflammatory Diseases Registry
- Melbourne Genomics Health Alliance
- JMF Centre Melbourne
