Diagnosis and Development

Acquire and rapidly translate new knowledge into clinical practice to improve patient management.

Our emphasis is on the research and development of unique technologies to improve services provided by Victorian Clinical Genetic Services (VCGS) Pathology, a wholly-owned subsidiary of Murdoch Children's Research Institute. We comprise interdisciplinary researchers, psychologists, students and diagnostics staff who interact on many levels.

Using the clinical resources of the VCGS Clinical Genetics group, Cytogenetics, Molecular Genetics and Newborn Screening laboratories, the group focuses on the neurogenetics and epigenetics of disorders related to the FMR1 gene. Mutations of this gene, which handles normal cognitive development and female fertility, can lead to Fragile X Syndrome, autism, premature ovarian failure, developmental delay and other cognitive disorders.

We also focus on:

• diagnosis of chromosome abnormalities,
• non-invasive prenatal testing and organ transplantation research (kidney, heart, lung, bone marrow)
• assay development for population screening of Fragile X Syndrome.

Over the past five years, the group has produced several patent families, and high-impact publications and began several nationwide clinical trials on inventions expected to improve the diagnosis and management of children with Fragile X-related disorders or with organ transplants.

Our projects

A Novel, Simple, Universal Blood Test Based on Copy Number Variants for Organ Transplant Monitoring

This work aims to develop a non-invasive method of monitoring rejection of kidney transplants using DNA derived from plasma from the donor organ. This may replace some or all of the need for regular biopsy and assessment—the current monitoring method. We regard such an alternative as a major unmet need. The method should apply to any type of organ transplant. A collaboration with Dr Slater, Dr Bruno and clinical collaborators at the Austin hospital.

The FREE FX study—Developing new tests for fragile X: Aiming to improve outcomes for children and their families through earlier diagnosis.

The main aim of this study is to trial several new highly accurate laboratory methods that can tell us about a person’s level of the FMR1 gene activity. The aim is to determine how soon after birth these tests can predict intellectual disabilities, behavioural problems and autism in children and adults who have expansions in the FMR1 gene. This is a collaborative study between Murdoch Children's Research Institute, La Trobe University, RCH Department of Psychology, University of Melbourne, Hunter Genetics and INTA Fragile X Centre in Chile, funded in part by NHMRC, Pierce Armstrong Trust, Royal Children’s Hospital Foundation, Marian & EH Flank Trust and the Chilean Government. The primary recruitment and assessment centres are in the Royal Children’s Hospital, Victoria and Hunter Genetics, NSW, Australia and INTA CDTSXF Santiago, Chile.

Epigenotype-phenotype relationships in FMR1-related disorders

This is an NHMRC supported prospective cohort study focusing on the characterisation of a novel epigenetic boundary and long-range epigenetic modifications specific to FMR1 expansion carriers with behavioural and cognitive disorders, with implications for treatment based on the reversal of specific epigenetic modifications at the FMR1 locus.

Improved absolute quantification of RNA toxicity in FMR1 premutation related disorders.

This study aims to validate for the first time the use of a new droplet digital test to predict an increased risk of developing early or late-onset disorders. RNA toxicity related to the FMR1 gene can link to late-onset disorders and early onset development problems and quantifying this toxicity to predict the likelihood of these disorders occurring is what this test aims to achieve. 

Funding

• Roche Organ Transplant Research Fund (ROTRF) 
• National Health and Medical Research Council
• Pierce Armstrong Foundation
• The Royal Children’s Hospital Foundation
• Marian & EH Flank Trust
• Chilean Government PhD scholarship

Collaborations

National

• Austin Hospital, Department of Nephrology
• The Royal Children’s Hospital, Department of Psychology
• The Royal Melbourne Hospital, Department of Nephrology
• Alfred Hospital, Department of Haematology
• La Trobe University
• Monash University
• Hunter Genetics
• The University of Melbourne
• Fragile X Alliance

International

• INTA - Instituto de Nutrición y Tecnología de los Alimentos, Chile
• Greenwood Genetic Centre, USA
• The University of California, Davis, USA

Featured publications

• Analysis of the Prader-Willi syndrome imprinting center using droplet digital PCR and next-generation whole-exome sequencing. 2019
  
  
• Assessing a hyperarousal hypothesis of insomnia in adults with autism spectrum disorder. 2019
  
  
• Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles. 2019
  
  
• Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features. 2019
  
  
• Accuracy of NEXUS II head injury decision rule in children: a prospective PREDICT cohort study. 2018