The study shows the functions of the BICRA gene in neural development in humans, flies

Reviewed by Emily Henderson, B.Sc.November 23, 2020

Doctors and scientists are constantly looking for new disease genes that can help them understand why patients have undiagnosed medical problems. Often the first clues come from genetic tests that reveal a change or mutation in a gene that they see in a child but not his parents.

This is exactly what led to a new study published today on American Journal of Human Genetics.

A multidisciplinary group including researchers from Baylor College of Medicine, Dana-Farber Cancer Institute and other institutions identified the BICRA gene as a new disease gene involved in a neurodevelopmental disorder and found evidence that BICRA works in neural development in humans. and in flies.

The findings provide answers to families and reveal new insights into how BICRA works for doctors and scientists, enabling the development of personalized medical plans for patients in the future.

BICRA mutations are associated with human neurodevelopmental disorders

The first patient identified by the researchers had undiagnosed neurological defects, including neurodevelopmental delay and other features similar, but not identical, to those seen in patients with Coffin-Siris syndrome. Genetic studies revealed that the patient was a carrier of a mutation in the BICRA gene.

“With the help of the online gene matching tool GeneMatcher, researchers found 11 other patients with similar conditions carrying variants of the BICRA gene,” said co-correspondent author Dr Hugo Bellen, Distinguished Service Professor of genetics. molecular and human at Baylor member of the Jan and Dan Neurological Research Institute at Texas Children’s Hospital.

In all 12 cases, the BICRA mutations were new in patients; they were not inherited from their parents. Some of the mutations led to the loss of function of the BICRA protein.

“Further analysis showed that BICRA mutations can cause disease in a dominant way: a mutation of only one of two copies of the BICRA gene in the genome is enough to cause disease,” said co-first author Dr Scott Barish. , a postdoctoral associate in the Bellen laboratory.

This work was performed in collaboration with Dr. Cigall Kadoch’s laboratory at the Dana-Farber Cancer Institute and Harvard Medical School.

Zebrafish and fruit flies link BICRA to neural development

To investigate the potential connection of the BICRA gene with the characteristics seen in patients, the researchers turned to zebrafish and fruit flies.

“We conducted the work with zebrafish in collaboration with the Undiagnosed Disease Network Zebrafish Core run by Dr. Monte Westerfield and Dr. John Postethwait at the University of Oregon. They made a mutation in BICRA’s version of zebrafish. that mimicked the mutation in one of the patients, “Barish said. “The mutation-carrying zebrafish showed a craniofacial defect similar to the facial features seen in the patients.”

“In fruit flies, we have shown that BICRA is expressed in neuronal and glia nuclei, in both larval and adult brains,” said Bellen, who is also a researcher at the Howard Hughes Medical Institute in Baylor.

Identifying BICRA as a disease gene can increase the rate at which other disease genes are identified. “

Daryl Scott, co-author of the study, associate professor of molecular and human genetics, Baylor College of Medicine