Scientists have identified mutations in the DENND5A gene that cause severe neurodevelopmental issues in infants, leading to improper brain cell division during development. This discovery, made through a study involving genetic samples from patients, offers families crucial information for diagnosis and family planning.
Scientists identify gene mutations that cause debilitating neurodevelopmental problems in infancy. Image Credit: The Neuro (Montreal Neurological Institute-Hospital)
Shortly after Kelly Cervantes’ daughter Adelaide was born, she started having terrible seizures. Doctors were unable to give her a solution, or even a cause.
We never had an overarching diagnosis for her, which was extraordinarily frustrating and isolating. If we did, we could join groups or talk to people who had various symptoms in common. We also had no idea what her prognosis looked like, or if we could have other children.”
Kelly Cervantes, Citizens United for Research in Epilepsy (CURE)
Her health deteriorated over time, and tragically, five days before turning four, she passed away.
She never really progressed past about a three-to-six-month physical development, and we are not entirely sure where she was intellectually. She was incredible but her life was really challenging and really hard.”
Kelly Cervantes, Citizens United for Research in Epilepsy (CURE)
Cervantes had registered her daughter in an unidentified illness study program. She received a call asking whether she would be interested in taking part in a study being undertaken at The Neuro following the death of her daughter. The study was published in the journal Nature Communications.
The investigators examined Adeliade's samples and those of 21 other patients with the illness. Through the use of the participant's genetic code to cultivate stem cells in a dish, the researchers discovered that abnormalities in a gene called DENND5A cause dysfunction, which prevents brain cells from correctly dividing throughout development. As a result, the growing brain has fewer stem cells, which shortens the critical period during which the brain forms in the embryo.
The discovery gives relatives of those who suffer from this uncommon ailment peace of mind. To help family members make educated decisions regarding family planning, it also made it possible for them to be tested for the mutations.
Genetic counselors, for instance, can advise prospective parents who carry the mutation to have their partners tested genetically and provide information on the condition's likelihood of being passed on.
With this study's knowledge, the mutation may one day be rectified thanks to developments in genome editing technology. Even though it would be years away at most, Cervantes says it would give her peace to know that her daughter helped find a solution.
Maybe someday down the road, the next Adelaide will have a treatment, and there will be an answer for that family. And how incredible is that to think, that my baby girl had a hand in that?”
Kelly Cervantes, Citizens United for Research in Epilepsy (CURE)
Genetic cause found for a rare epileptic encephalopathy
Video Credit: The Neuro (Montreal Neurological Institute-Hospital)
Source:
Journal reference:
Banks, E., et al. (2024) Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy. Nature Communications. doi.org/10.1038/s41467-024-51310-z.
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