PARIS — A new gene expressed in the fetal brain and associated with certain malformations of the cerebral cortex has been discovered by researchers at France's Institut National de la Santé et de la Recherche Médicale (INSERM).
Called Doublecortine, the gene plays a role in neuronal migration and is associated with X-linked subcortical laminar heterotopia (X-SCLH) and lissencephaly (LIS) syndrome, two types of cortical malformation that are known to be responsible for serious forms of epilepsy associated with retarded mental development. The former is most commonly found in girls, while lissencephaly mainly affects boys. In both cases the condition is characterized by an abnormally formed cortex.
The fact that these abnormalities are transmitted solely by mothers to their children and that the consequences can be severe in boys suggested that the X-SCLH/LIS syndrome was essentially transmitted genetically and was determined by sex. To test this hypothesis, the research team, led by Jamel Chelly, based at Cochin Hospital, in Paris, monitored the transmission of localized genetic markers on the X chromosome of individuals from three families in which there were both girls suffering from X-SCLH and boys from LIS.
The resulting genetic map confirmed the defective gene responsible for these cortical malformations is located on the sex (X) chromosome. After sequencing the gene, the researchers detected irregularly occurring mutations in two-thirds of the 17 subjects suffering from X-SCLH or LIS, demonstrating the key role played by the Doublecortine gene in this syndrome.
According to the research team, this discovery marks a further step in understanding the molecular mechanisms behind the development of the brain and provides a pre-natal diagnostic tool for identifying people at risk. INSERM filed a patent application for the discovery last November.