The team at the Thorax Institute: Dr. Stéphane Bézieau, Dr. Wallid Deb, Dr. Frédéric Ebstein. © Thorax Institute

Researchers at the Thorax Institute (Nantes University, Inserm, CNRS, CHU de Nantes) have made a significant breakthrough in understanding the causes of neurodevelopmental disorders in children.

In collaboration with international researchers, a team from Nantes led by Dr. Frédéric Ebstein and Dr. Stéphane Bézieau has identified “a new defective gene responsible for a rare form of intellectual disability, associated with behavioral disorders and recurrent obesity in young children.” These findings have been published in the scientific journal American Journal of Human Genetics.

A faulty molecular shredder causing the disease

The Nantes geneticists have discovered ten mutations on the PSMD11 gene that strongly affect the action of the proteasome: this crucial macromolecular complex normally acts as a molecular shredder, eliminating damaged or unnecessary proteins so that they can be replaced by new ones. Children carrying these mutations that disrupt the action of the proteasome are likely to accumulate toxic proteins, which will have consequences on their neurodevelopment. “Our study confirms the cause-and-effect relationship between proteasome dysfunction and the onset of neurodevelopmental disorders,” explains Wallid Deb, the first author.

Nearly half of children with neurodevelopmental disorders do not receive a precise diagnosis, leaving families in uncertainty and despair. The discovery by the Nantes researchers represents a significant advancement for patients “carrying a mutation of the PSMD11 gene.” Their condition is now classified by the Nantes researchers under the concept of “neurodevelopmental proteasomeopathies.” With this additional knowledge, there is hope of developing potential treatments in the long term.

This breakthrough by the Nantes geneticists opens up new possibilities for understanding and treating neurodevelopmental disorders in children, providing hope for affected families and paving the way for further research in this important field of study.