Breakthrough in cleft lip and palate research

June 8, 2018 by Neura Media, University of New South Wales
Breakthrough in cleft lip and palate research
Associate Professor Tony Roscioli from NeuRA and UNSW Sydney. Credit: University of New South Wales

Four genes have been identified which work together to cause cleft lip and palate, in an international research collaboration with researchers from UNSW Sydney and the University of Washington.

The , associated for the first time with 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. The NHMRC-funded project was led by Associate Professor Tony Roscioli from Neuroscience Research Australia (NeuRA), UNSW Sydney and Sydney Children's Hospital, Randwick; and Professor Timothy Cox, from Seattle Children's Research Institute and the University of Washington School of Medicine in the USA.

Representing about 70 per cent of lip and palate cases worldwide, non-syndromic cleft lip and palate typically occur 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. These genes are known to encode proteins that work together in a network, providing important insight into the biological basis of the 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 3 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 Professor 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 Professor Roscioli.

"What we were seeking to identify in this study was whether single genes could cause a cleft lip or palate in families where there were multiple affected people.

Breakthrough in cleft lip and palate research
Credit: University of New South Wales

"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."

Commenting on their breakthrough, Professor Timothy Cox said prior studies had focused on using large numbers of affected individuals without an obvious family history, searching for common genetic variants that are associated with an increased risk of a child being born with a cleft.

"We reasoned that non-syndromic cleft lip and palate occurring in families is more likely to be caused by a single rare variant that we can pinpoint using available new sequencing technologies," said Professor Cox.

"The genetic pathway that emerged from these data gathered through collaboration with clinical teams from around the world is arguably one of the most significant advances in cleft lip and palate genetics in the last 15 years."

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

"Importantly, we also showed that some affected individuals in this study had a gene variant which was inherited from neither parent – that is, it likely arose spontaneously in the affected individual during early development – and therefore the parents were able to be reassured of a very low chance of having another affected child," A/Prof Roscioli said.

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.

Timothy Cox is a senior Professor in the Department of Paediatrics at the University of Washington School of Medicine, and a member of the Seattle Children's Research Institute's Center for Developmental Biology and Regenerative Medicine and Seattle Children's Craniofacial Centre. His team seeks to understand how genes and maternal nutritional factors interact to control the formation of the unborn child's face and how these factors impact a child's risk of being born with cleft lip and palate. He hopes his research will lead to innovative approaches to reduce the severity or incidence of cleft lip and palate in newborns that carry a genetic predisposition to the birth defect.

Explore further: Primary care pediatrician vital for cleft lip/palate care

Related Stories

Primary care pediatrician vital for cleft lip/palate care

April 25, 2017
(HealthDay)—For children with cleft lip and/or cleft palate (CL/P), the primary care pediatrician has an important role, according to a clinical report published online April 24 in Pediatrics.

Cleft palate discovery in dogs to aid in understanding human birth defect

April 7, 2014
UC Davis School of Veterinary Medicine researchers have identified the genetic mutation responsible for a form of cleft palate in the dog breed Nova Scotia Duck Tolling Retrievers.

New gene responsible for cleft lip and palate syndrome identified

December 19, 2013
An international team led by researchers from Karolinska Institutet in Sweden has identified a new gene related to the Van der Woude syndrome, the most common syndrome with cleft lip and palate. The study is published in ...

Epigenetics could help diagnose different types of cleft

June 15, 2017
Cleft lip and/or palate are common birth defects and affect around 15 in every 10,000 births in Europe. New research by the University of Bristol from the largest study of cleft lip and/or palate in the world, the Cleft Collective, ...

Babies with cleft lip likely to have normal adulthood: study

September 27, 2016
(HealthDay)—Cleft lip is a relatively common birth defect that can be surgically repaired, and new research suggests that parents don't have to worry about long-term health problems for these children.

Scientists identify mutation associated with cleft palate in humans and dogs

October 19, 2014
Scientists studying birth defects in humans and purebred dogs have identified an association between cleft lip and cleft palate – conditions that occur when the lip and mouth fail to form properly during pregnancy – and ...

Recommended for you

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Targeting the engine room of the cancer cell

June 18, 2018
Researchers at Columbia University Irving Medical Center (CUIMC) have developed a highly innovative computational framework that can support personalized cancer treatment by matching individual tumors with the drugs or drug ...

Scientists learn more about how gene linked to autism affects brain

June 18, 2018
New preclinical research shows a gene already linked to a subset of people with autism spectrum disorder is critical to healthy neuronal connections in the developing brain, and its loss can harm those connections to help ...

161 genetic factors for myopia identified

June 15, 2018
The international Consortium for Refractive Error and Myopia (CREAM) recently published the largest-ever genetic study of myopia in Nature Genetics. Researchers from the Gutenberg Health Study at the Medical Center of Johannes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.