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 male 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 DOCK8 gene from the critical 9p deletion region and determined that the longest isoform of the DOCK8 gene is truncated in both patients. Furthermore, the DOCK8 gene is expressed in several human tissues, including adult and fetal brain. Recently, a role for DOCK8 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 DOCK8 gene may contribute to some cases of autosomal dominant mental retardation.
Griggs
Bradley L
BL
J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA; Department of Genetics & Biochemistry, Clemson University, Clemson, SC 29634, USA.
Ladd
Sydney
S
Saul
Robert A
RA
DuPont
Barbara R
BR
Srivastava
Anand K
AK
D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D014178:Translocation, Genetic
C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors