Québec siblings with rare orphan disease lead to discovery of rare genetic diseases

Mutations in a gene involved in brain development have led to the discovery of two new neurodevelopmental diseases by an international team led by researchers at McGill University and CHU Sainte-Justine Research Center.

The first clues about the rare disorder arose after doctors were unable to diagnose why two siblings from Québec City were experiencing seizures and neurodevelopmental deficits. Desperate, the children’s family turned to Carl Ernst at the Douglas Mental Health University Institute in Montreal for answers.

Ernst, who is also a professor in McGill’s Department of Psychiatry, and his team used harvested skin cells from the toddlers and “reprogrammed” them to assume a stem cell-like state—induced pluripotent stem cells (iPSC). By making neurons from the iPSCs and comparing them to those of healthy individuals, the researchers found that they did not develop properly. Upon further investigation, they discovered a potential culprit: the family carried a mutation in ACTL6B – an epigenetic regulator implicated in neuronal development.