A novel gene, Doublecortin, expressed in the fetal brain and involved in certain malformations of the cerebral cortex, has just been identified by the Dr. Jamel Chelly's team at INSERM 129 (directed by Professor Axel Kahn, Paris, France). This should provide insight into how the brain develops and yield a tool for prenatal diagnosis in persons at risk. This work is published in Cell (January 9 th 1998).
In the early phases of embryonic development, the cerebral cortex is formed by the migration of successive waves of neurons. It is well established that defective neuronal migration can lead to severe cortical malformations, but the factors involved in this phenomenon are poorly understood. An interesting candidate is the Doublecortin gene, which has just been identified by Vincent des Portes and coworkers, who are part of the team headed by Dr. Jamel Chelly at INSERM 129 in Paris (directed by Professor Axel Kahn). In addition, the team showed that this gene is involved in some types of cortical malformations named the X-SCLH/LIS syndrome.
The X-SCLH/LIS syndrome was first described by French neuropaediatricians at Saint-Vincent de Paul hospital (Paris) and Reims, and is associated with severe forms of epilepsy and mental retardation. This syndrome consists of two similar malformations of the cerebral cortex known as subcortical laminar heterotopia (SCLH) and lissencephaly. The former is more common in girls, while the latter mainly affects boys. Subjects with this rare syndrome have an abnormally formed cortex.
The observation that the syndrome is exclusively transmitted by the mother, together with the severe forms affecting boys, pointed to sex-linked dominant genetic transmission.
The INSERM team first examined the hereditary transmission of genetic markers
located on the sex chromosome X in members of three families in which girls had
SCLH and boys had lissencephaly. This genetic mapping approach by linkage
analysis allowed them to confirm th
Contact: Axel Kahn
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French National Institute for Health and Medical Research (INSERM)