Topic: PCDH19

Mutations in the X-chromosome gene PCDH19 cause Developmental and Epileptic Encephalopathy-9 (DEE9), a rare neurodevelopmental disorder characterized by epilepsy, autism spectrum disorder and cognitive impairment. DEE9 is characterized by a peculiar gender preference, affecting mainly heterozygous females.Recently, it was found that in vivo mosaic expression of Pcdh19 impairs the maturation and migration of neurons and the GABAergic circuitry, leading to defects of excitation/inhibition (E/I) balance. Since the GABAergic parvalbumin interneurons (PVIs) are powerful regulators of pyramidal neu

Developmental and Epileptic Encephalopathy 9 (DEE9) is a debilitating neurological condition with no effective cure characterized by epilepsy, intellectual disability and autism. DEE9 is due to mutations in the X-chromosome gene PCDH19 that encodes protocadherin-19 (PCDH19), a cell adhesion molecule. We recently reported that PCDH19 undergoes an activity-dependent proteolytic cleavage that generates a cytosolic C-terminal fragment (CTF), which goes in the nucleus and regulates the expression of a subset of immediate early genes in primary hippocampal neurons.The aim of this project is to inves