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. Doctors were unable to diagnose why two siblings from Québec City were experiencing seizures and neurodevelopmental deficits.
Dr. Campeau and Professor Ernst were working on the same mutations so the researchers decided to join to study this disease.
Ernst 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.
Around the same time, Dr. Philippe Campeau was also studying ACTL6B mutations identified in two families as part of an epilepsy genome study led by his colleagues Dr. Jacques Michaud and Dr. Elsa Rossignol. With the help of Julie Lessard, an ACTL6B expert from the Institute for Research in Immunology and Cancer, Dr. Campeau was mapping how ACTL6B mutations affected protein interactions.
Thanks to new research tools such as iPSC and CRISPR gene editing technology, the study showed that ACTL6B mutations caused a dysregulation of other genes important for the development of dendrites, branched projections of neurons that play a critical for communication between brain cells.
ACTL6B recessive