identification of a new responsible gene

L’alternating hemiplegia infancy (HAE) is a very rare neurodevelopmental disorder characterized by periodic hemiplegia, persistent developmental delay and cognitive deficit. The major early sign is the occurrence of repeated episodes ofhemiplegia from a few minutes to several days, sometimes affecting one side of the body, sometimes the other. Several factors can trigger acute episodes: stress, exposure to water, physical activity, light variations and certain foods. To date there is no specific treatment HAE which affects less than one in 100,000 children each year. Patient care is symptomatic. To date, only one responsible gene has been identified.

Discovery of a second causative gene

Scientists from Trinity College Dublin, Inserm, Université Paris Cité and AP-HP at the Imagine Institute at Necker Hospital in Paris have identified the CLDN5 geneas being responsible for alternating hemiplegia in children in two unrelated cases of EDT in France. The protein produced by this gene, claudin-5, is essential for maintaining the integrity of the blood-brain barrier which isolates and protects the brain from the rest of the body’s functioning.

Unexplainedly, the mutated form of the protein transforms the barrier into a selective channel for negatively charged ions. The ionic compositions of the brain are probably modified in these children, which constitutes a key factor in the disease.

In addition to bringing new knowledge to this disease and hoping for better care for children with this mutation, this work could have repercussions on the fundamental understanding of the junction protein that forms the blood-brain barrier.