Researchers Find Novel Genes Linked To Rare Childhood Diarrhoea

The rare condition called CODE (congenital diarrhoea and enteropathies) disrupts the function of cells in the intestine, causing diarrhoea. It also prevents infants from absorbing the nutrients they need to grow and thrive.

The team from The Hospital for Sick Children (SickKids) conducted genome sequencing on 129 infants with suspected CODE.

The scientists characterised the function of novel CODE genes using advanced computational methods and zebrafish models

The analysis was remarkably successful, providing a diagnosis for 48 per cent of cases.

The findings, published in the New England Journal of Medicine, found three new genes associated with CODE -- GRWD1, MYO1A , and MON1A -- and provided answers to 62 families.

“Undiagnosed infantile diarrhoea can be fatal, but even when it isn't, early diagnosis of rare conditions can help provide much-needed answers for families,” said Dr. Aleixo Muise, Staff Gastroenterologist and Senior Scientist in the Cell and Systems Biology programme at SickKids.

“As a result of this study, we can now provide a diagnosis to more families and move closer to precision treatments tailored to their child's specific genetic variant,” Muise added.

ODEs are associated with high morbidity and mortality. Although the treatment of these disorders is largely supportive, emerging targeted therapies based on genetic diagnoses include specific diets, pharmacologic treatments, and surgical interventions.

A genetic diagnosis alone can provide relief to many families, said the team.

They noted that understanding the genetic and functional underpinnings of the conditions, including three new pathways, can also move scientists closer to targeted treatments.

In addition to the genes, in the case series of 129 infants with suspected congenital diarrhoeal disorders, the team identified causal variants, including a new founder NEUROG3 variant, in 62 infants (48 per cent).

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