A handful of patients who suffer from seizures and mild intellectual disability have now led the way to insights about how one piece of regulatory DNA controls development of a section of the human cortex. Imaging the brains of these patients, Bae et al. (see the Perspective by Rash and Rakic) observed malformations on the surface folds in a brain region that includes “Broca's area,” the main region underlying language. The three affected families shared a 15–base pair deletion in the regulatory region of a gene, GPR56, which encodes a G protein–coupled receptor required for normal cortical development that is expressed in cortical progenitor cells.
B.-I. Bae, I. Tietjen, K. D. Atabay, G. D. Evrony, M. B. Johnson, E. Asare, P. P. Wang, A. Y. Murayama, K. Im, S. N. Lisgo, L. Overman, N. Šestan, B. S. Chang, A. J. Barkovich, P. E. Grant, M. Topçu, J. Politsky, H. Okano, X. Piao, C. A. Walsh, Evolutionarily dynamic alternative splicing of GPR56 regulates regional cerebral cortical patterning. Science 343, 764–768 (2014). [Abstract] [Full Text]