The Centre for Research Excellence in Neurocognitive Disorders (CRE-NCD), led by Associate Professor Tony Roscioli, aims to transform diagnosis and management of severe intellectual disability (also known as neurocognitive disorders) through the application of genomic technologies, including whole exome sequencing (WES) and whole genome sequencing (WGS).

Neurocognitive disorders are one of the largest unmet challenges in Australian healthcare. They are common, with approximately 3000 children born annually with a moderate to severe neurocognitive disorder. In addition, these disorders have high management costs and recur frequently within families.

Despite the significant unmet need for treatments for neurocognitive disorders, it has been very difficult to make a genetic diagnosis in these disorders, and to develop effective therapies. This is because neurocognitive disorders are remarkably genetically diverse: more than 1200 genes have so far been associated with them, and it is estimated that over 1000 more are yet to be identified. A genetic or molecular diagnosis with an accurate genotype-phenotype classification is essential for defining a cause for families, improving patient management, predicting recurrence risk, and for the successful design of targeted therapeutics. In the past, a clinical diagnosis and single gene-by-gene tests were relied upon to diagnose neurocognitive disorders. These were only partially successful. Whole genome sequencing can triple the current diagnostic rate in people with moderate and severe neurocognitive disorders from 15 – 20% to over 60%, as well as identify new genes not previously known to be associated with such disorders.

This substantial increase in the rate of diagnosis will have a positive impact on many families across Australia. For a child to receive a genetic diagnosis early in life is a powerful thing: it gives parents an explanation of what caused the disorder, often a new non-inherited change with a very low chance of happening again. A specific diagnosis also helps families and doctors to plan for the future healthcare needs of children with neurocognitive disorders – and makes access to resources easier. The aim is that within the next 5 years, all Australians with NCDs will have access to genomic testing, achieving a diagnosis in >50%.

Beyond the transformation in the diagnosis of neurocognitive disorders, the new CRE also aims to:

• Understand how newly identified genetic variants contribute to disease;

• Bring together genomic information and clinical information, including 3D analysis of facial shape, so as to identify neurocognitive disorder subgroups that could respond differently to treatment;

• Investigate health economic models to contribute to policies to maximize resources for families and

• Investigate pharmacological treatment options across the identified subgroups.

The CRE-NCD team comprises researchers and clinicians with internationally recognised leadership and track records in neurogenetics research, genomics, bioinformatics, functional

analysis, health economics and clinical practice.

The chief investigators in the CRE team are as follows:

• CIA Associate Professor Tony Roscioli: Staff Specialist in Clinical Genetics, Sydney Children’s Hospital, Group Leader Neurogenomics, Neuroscience Research Australia, Sydney

• Professor Jozef Gecz: Head, Neurogenetics Research Program, the University of Adelaide at the Women’s and Children’s Hospital, Adelaide

• Dr Michael Field: Clinical Geneticist and Director, Genetics of Learning Disability, Hunter Genetics, Newcastle

• Dr Deborah Schofield: Director, Centre for Economic Impacts of Genomic Medicine & Professor and Chair of Health Economics, Department of Economics, Macquarie University, Sydney

• Associate Professor Michael Buckley: Genetic Pathologist and Clinical Director, SEALS Genetics Laboratory, Prince of Wales Hospital, Sydney

• Professor Kathryn North: Clinical Geneticist, Child Neurologist and Director, Murdoch Children’s Research Institute and Victorian Clinical Genetics Service, Melbourne

• Associate Professor Marcel Dinger: Head of Kinghorn Centre for Clinical Genomics, Garvan Institute for Medical Research, Darlinghurst

• Professor John Christodoulou: Chair of Genomic Medicine, Murdoch Childrens Research Institute, and Dept of Paediatrics, Melbourne Medical School, University of Melbourne, Melbourne

• Professor David Amor: Clinical Geneticist and Director, Victorian Clinical Genetics Services, Murdoch Children Research Institute, Melbourne

• Associate Professor Gareth Baynam: Clinical Geneticist Genetic Services of Western Australia (GSWA), Perth