Dedicator of cytokinesis 8 is disrupted in two patients with mental retardation and developmental disabilities

We have identified disruptions in the dedicator of cytokinesis 8 gene, DOCK8, in two unrelated patients with mental retardation (MR). In one patient, a mate with MR and no speech, we mapped a genomic deletion of approximately 230 kb in subtelomeric 9p. In the second patient, a female with mental retardation and ectodermal dysplasia and a balanced translocation, t(X;9) (q13. 1;p24), we mapped the 9p24 breakpoint to a region overlapping with the centromeric end of the 230-kb subtelomeric deletion. We characterized the DOCKS gene from the critical 9p deletion region and determined that the longest isoform of the DOCKS gene is truncated in both patients. Furthermore, the DOCKS gene is expressed in several human tissues, including adult and fetal brain. Recently, a role for DOCKS in processes that affect the organization of filamentous actin has been suggested. Several genes influencing the actin cytoskeleton have been implicated in human cognitive function and thus a possibility exists that the rare mutations in the DOCKS gene may contribute to some cases of autosomal dominant mental retardation. (c) 2007 Elsevier Inc. All rights reserved.