NeuRA Magazine #26

Research

BREAKTHROUGH IN CLEFT LIP AND PALATE RESEARCH

An international research collaboration between Australia and the USA, led by Associate Professor Roscioli at NeuRA has identified new genes that cause cleft lip and palate. The genes, associated for the first time with cleft lip and palate, encode proteins that work together in a network, providing important insights into the biological basis of one of the most common physical malformations.

Representing about 70 per cent of cleft lip and palate cases worldwide, non-syndromic cleft lip and palate typically occurs in isolation without other physical abnormalities. This craniofacial malformation has long been considered to be caused by a combination of many common genetic variants and environmental factors, each contributing a small amount to the risk of a child being born with a cleft.

Using next generation sequencing, the research team identified variants in four new genes, each representing a primary cause of non-syndromic cleft lip and palate. Variants in these genes were found to account for 15 per cent of the families who took part in the study and in nearly three per cent of a second, larger group of smaller families and isolated cases.

Published in the American Journal of Human Genetics, the study provides the first evidence that a significant number of non-syndromic clefts have a single gene basis and not a complex basis as previously thought.

Associate Prof Tony Roscioli said cleft lip/palate is one of the most common human malformations, occurring in one in 800 children.

“That equates to about 250 Australian children each year and one affected child born every three minutes worldwide,” said Associate Prof Roscioli.

“Knowing the genes and the way these impact lip and palate formation opens the door for further research to understand how these genes work and to develop treatments.”

Cleft lip and cleft palates are repaired with corrective surgery. Future research will investigate the biology and link the findings to potential therapies. These discoveries will allow geneticists to provide more accurate information to families.

Associate Professor Tony Roscioli is a specialist in clinical genetics at the Sydney Children’s Hospital and leads the Sydney Partnership for Health Education Research and Enterprise (SPHERE) GenomeConnect clinical academic stream. At NeuRA he leads the Centre for Research Excellence in Neurocognitive Disorders where he endeavours to transform the diagnosis and management of intellectual disability through genomics.

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LEAD!- Leveraging Evidence into Action on Dementia

Currently, there is no effective treatment for dementia, highlighting the urgent need to preventing more cases through evidence-based strategies for risk reduction. As there is an overlap between the risk factors for dementia and other preventable non-communicable diseases including stroke, diabetes, and heart disease, it is important to build upon proven risk-reduction strategies. What is LEAD? LEAD! is a project funded by the NHMRC Boosting Dementia Research Grant led by Professor Kaarin Anstey. It involves an international collaboration between leading academics, clinicians, consumers, and community members. Organisations involved include the Department of Health, WHO, Dementia Australia, Alzheimer’s Disease International, Diabetes Australia, and Heart Foundation. The project aims to translate dementia research and implement evidence-based strategies for dementia risk reduction to individuals, communities, and healthcare centres. Three workstreams The project has three concurrent workstreams over five years: Development, Implementation, and Evaluation and adoption. The Development stream, led by Professor Kaarin Anstey and Associate Professor Peters, focuses on building a new tool for predicting dementia and other non-communicable diseases including stroke, diabetes or myocardial infarction. The tool will be available to the public, researchers and clinicians. It will save clinical assessment time, accurately predict multiple outcomes and will be more acceptable in comparison to using individual tools for each disease outcome. The Implementation stream led by Professor Nicola Lautenschalger’s team at the University of Melbourne, will develop strategies to support the implementation of dementia risk reduction evidence by engaging with consumers, clinicians, policy makers, and the public. The stream will develop strategies for incorporating the new risk assessment tool into various technological platforms (e.g., websites or apps). The Evaluation and adoption stream, led by Professor Anstey and in collaboration with Professor Louisa Jorm and Dr Heidi Welberry at UNSW, focuses on measuring trajectories of Australian’s national risk factor profiles for multiple chronic diseases. Collaboration with key stakeholders including the WHO will help build an evaluation framework and methodology for implementing evidence on dementia risk reduction based on WHO guidelines at national level and in the global context.
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