TY - JOUR T1 - Functional genetic characterization by CRISPR-Cas9 of two enhancers of <em>FOXP2</em> in a child with speech and language impairment JF - bioRxiv DO - 10.1101/064196 SP - 064196 AU - R. Torres-Ruiz AU - A. Benitez-Burraco AU - M. Martínez-Lage AU - S. Rodríguez-Perales AU - P. García-Bellido Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/08/02/064196.abstract N2 - Mutations in the coding region of FOXP2 are known to cause speech and language impairment. Microdeletions involving the region downstream the gene have been also associated to speech and cognitive deficits. We recently described a girl harbouring a complex chromosomal rearrangement with one breakpoint downstream the gene that might affect her speech and cognitive abilities via physical separation of distant regulatory DNA elements. In this study, we have used highly efficient targeted chromosomal deletions induced by the CRISPR/Cas9 genome editing tool to demonstrate the functionality of two enhancers, FOXP2-Eproximal and FOXP2-Edistal, located in the intergenic region between FOXP2 and its adjacent MDFIC gene. Deletion of any of these two functional enhancers in the neuroblastomic cell line SK-N-MC downregulates FOXP2 and decreases FOXP2 protein levels, conversely it upregulates MDFIC and increases MDFIC protein levels. This suggests that both regulatory elements may be shared between FOXP2 and MDFIC. We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting speech and language. ER -