Discovery of rare genetic diseases in Quebec siblings suffering from an orphan disease

Discovery of ACTL6B gene mutations provides information on brain development

By studying the mutations of a gene that participates in brain development, an international team led by researchers at McGill University and the CHU Sainte-Justine Research Center has uncovered two new neurodevelopmental diseases.

The first clues leading to this discovery were found after Quebec doctors failed to identify the cause of seizures and neurodevelopmental deficits in two siblings. In desperation, the children's parents turned to Carl Ernst from the Douglas Mental Health University Institute in Montreal.

Professor Ernst, who teaches in the Department of Psychiatry at McGill University, and his team have "reprogrammed" skin cells taken from two toddlers to transform them into stem cells. They then induced these induced pluripotent stem cells (CSPI) to differentiate into neurons, which they compared to healthy neurons, to find that reprogramming neurons had not developed normally. Further analysis has found a possible cause: the presence of a mutation in the ACTL6B gene - an epigenetic regulator involved in neuronal development - in affected family members.

At the same time, Dr. Philippe Campeau, a geneticist at the CHU Sainte-Justine Research Center and a professor at the Universit