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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Abdominal muscle stimulation to improve bowel function in spinal cord injury

Bowel complications, resulting from impaired bowel function, are common for people living with a spinal cord injury (SCI). As a result, people with a SCI have high rates of bowel related illness, even compared with those with other neurological disorders. This includes high rates of abdominal pain, constipation, faecal incontinence and bloating. These problems lower the quality of life of people with a SCI and place a financial burden on the health system. A treatment that improves bowel function for people with a SCI should reduce illness, improve quality of life and lead to a large cost saving for health care providers. Bowel problems have traditionally been managed with manual and pharmacological interventions, such as digital rectal stimulation, enemas, and suppositories. These solutions are usually only partially effective, highlighting the need for improved interventions. The abdominal muscles are one of the major muscle groups used during defecation. Training the abdominal muscles should improve bowel function by increasing abdominal pressure. During our previous Abdominal FES research with people with a SCI, we observed that Abdominal FES appeared to lead to more consistent and effective bowel motion. However, this evidence remains anecdotal. As such, we are going to undertake a large randomised controlled trial to investigate the effectiveness of Abdominal FES to improve the bowel function of people with a SCI. This study will make use of a novel measurement system (SmartPill, Medtronic) that can be swallowed to measure whole gut and colonic transit time. We will also assess whether Abdominal FES can change constipation-related quality of life and the use of laxatives and manual procedures, as well as the frequency of defecation and the time taken. A positive outcome from this study is likely to lead to the rapid clinical translation of this technology for people living with a SCI.
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