Rare Disease

Rare Disease

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.

Acute Care Genomics

The Acute Care Genomics study is providing ultra-rapid genomic testing, with results available in less than 5 days, for around 250 babies and children in intensive care units across Australia, with the aim of providing diagnostic certainty and guiding acute care management.

Rapid genomic testing is only available at a handful of centres worldwide, and the Acute Care Genomics study is the first study to provide rapid testing for rare disease diagnosis at a national level.

The flagship is evaluating the diagnostic and clinical outcomes from ultra-rapid genomic sequencing; identifying the clinical and laboratory barriers to implementation and service impacts; and establishing the most cost-effective and efficient technology for the delivery of acute care genomics.

The Acute Care Genomics study has been established with support of The Royal Children’s Hospital Foundation, the Sydney Children’s Hospital Network and Australian Genomics.

Leads

A/Prof Zornitza Stark (clinical lead)
Victorian Clinical Genetics Services

Dr Sebastian Lunke (laboratory lead)
Victorian Clinical Genetics Services

 

Victoria

Prof John Christodoulou
Murdoch Children’s Research Institute

Dr Emma Krzesinski
Monash Health

Dr Matthew Hunter
Monash Health

A/Prof Sue White
Victorian Clinical Genetics Services

Victoria

A/Prof Tiong Tan
Victorian Clinical Genetics Services

Dr Katherine Howell
The Royal Children’s Hospital

Dr Lauren Akesson
The Royal Children’s Hospital

Dr Andrew Fennell
Monash Health

Dr Joy Lee
The Royal Children’s Hospital

Dr Heidi Peters
The Royal Children’s Hospital

Dr Michelle De Silva
Victorian Clinical Genetics Services

Sam Ayres
Victorian Clinical Genetics Services

Victoria

Gemma Brett
Victorian Clinical Genetics Services

Ivan Macciocca
Victorian Clinical Genetics Services

Lyndon Gallacher
Victorian Clinical Genetics Services

Dr Amanda Moody
The Royal Children’s Hospital

Dr George McGillivray
The Royal Women’s Hospital

Dr Anand Vasudevan
The Royal Women’s Hospital

A/Prof Christiane Theda
The Royal Women’s Hospital

Ella Wilkins
Victorian Clinical Genetics Services

New South Wales

Dr Jason Pinner
Sydney Children’s Hospital

Dr Sarah Sandaradura
The Children’s Hospital at Westmead

A/Prof Meredith Wilson
The Children’s Hospital at Westmead

Kirsten Boggs
Sydney Children’s Hospital Network

A/Prof Michael Buckley
NSW Health Pathology

A/Prof Tony Roscioli
Sydney Children’s Hospital

Prof Edwin Kirk
Sydney Children’s Hospital

Dr Annie Bye
Sydney Children’s Hospital

New South Wales

Dr David Mowat
Sydney Children’s Hospital

Dr Kevin Swil
Sydney Children’s Hospital

Dr Meredith Ward
The Children’s Hospital at Westmead

Dr Amit Trivedi
The Children’s Hospital at Westmead

Dr Kaustuv Bhattacharya
Sydney Children’s Hospital

Dr Lisa Ewans
Royal Prince Alfred Hospital

Ron Fleischer
Royal Prince Alfred Hospital

Dr Himanshu Goel
Hunter Genetics

Dr Nick Pigott
Sydney Children’s Hospital Network

Queensland

Dr Chirag Patel
Royal Brisbane and Women’s Hospital
Queensland Children’s Hospital

A/Prof Julie McGaughran
Genetic Health Queensland

Michael Quinn
Genetic Health Queensland

Melanie Tom
Genetic Health Queensland

Prof David Coman
Queensland Children’s Hospital

Dr Deepa Srinivasan
Queensland Children’s Hospital

Prof Luregn Schlapbach
Queensland Children’s Hospital

Dr Katherine White
Royal Brisbane and Women’s Hospital

South Australia

A/Prof Chris Barnett
Women’s and Children’s Hospital

Prof Jozef Gecz
University of Adelaide

Sarah Borrie
Women’s and Children’s Hospital

Anne Baxendale
Women’s and Children’s Hospital

  • Queensland Children’s Hospital
  • Royal Brisbane and Women’s Hospital
  • Sydney Children’s Hospital Randwick
  • The Children’s Hospital at Westmead
  • Westmead Hospital
  • The Royal Hospital for Women
  • Hunter Children’s Hospital
  • Royal Prince Alfred Hospital
  • The Royal Children’s Hospital
  • The Royal Women’s Hospital
  • Monash Health
  • Women’s and Children’s Hospital
  • Australian Genomics
  • The Royal Children’s Hospital Foundation
  • The Sydney Children’s Hospital Network

Relevant Publications

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.

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, J.M., Bombard, Y., Cornel, M.C., Fernandez, C.V., Junker, A.K., Plon, S.E., et al. (2018). Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application? Genet Med.

Cardiovascular Genetic Disorders

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

chILDRANZ: Interstitial and Diffuse Lung Disease in Children

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

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.

KidGen 'HIDDEN' Renal Genetics

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.

Neuromuscular Disorders

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

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.

KidGen Renal 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

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.

Neurodevelopmental Disability

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 Immunology

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