Psychology Commons^™

A Sequence Variant In Human Kalrn Impairs Protein Function And Coincides With Reduced Cortical Thickness, Derin J. Cobia, Theron A. Russell, Katherine D. Blizinsky, Michael Cahill, Zhong Xie, Robert A. Sweet, Jubao Duan, Pablo V. Gejman, Lei Wang, John G. Csernansky, Peter Penzes

Faculty Publications

Dendritic spine pathology is a key feature of several neuropsychiatric disorders. The Rac1 guanine nucleotide exchange factor kalirin-7 is critical for spine morphogenesis on cortical pyramidal neurons. Here we identify a rare coding variant in the KALRN gene region that encodes the catalytic domain, in a schizophrenia patient and his sibling with major depressive disorder. The D1338N substitution significantly diminished the protein's ability catalyze the activation of Rac1. Contrary to wild-type kalirin-7, kalirin-7-D1338N failed to increase spine size and density. Both subjects carrying the polymorphism displayed reduced cortical volume in the superior temporal sulcus (STS), a region implicated in schizophrenia. …