Disruption of Diacylglycerol Kinase Delta (DGKD) Associated with Seizures in Humans and Mice

Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
The American Journal of Human Genetics (Impact Factor: 10.99). 05/2007; 80(4):792-9. DOI: 10.1086/513019
Source: PubMed

ABSTRACT We report a female patient with a de novo balanced translocation, 46,X,t(X;2)(p11.2;q37)dn, who exhibits seizures, capillary abnormality, developmental delay, infantile hypotonia, and obesity. The 2q37 breakpoint observed in association with the seizure phenotype is of particular interest, because it lies near loci implicated in epilepsy in humans and mice. Fluorescence in situ hybridization mapping of the translocation breakpoints showed that no known genes are disrupted at Xp11.2, whereas diacylglycerol kinase delta (DGKD) is disrupted at 2q37. Expression studies in Drosophila and mouse suggest that DGKD is involved in central nervous system development and function. Electroencephalographic assessment of Dgkd mutant mice revealed abnormal epileptic discharges and electrographic seizures in three of six homozygotes. These findings implicate DGKD disruption by the t(X;2)(p11.2;q37)dn in the observed phenotype and support a more general role for DGKD in the etiology of seizures.

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Available from: David J Harris, Aug 16, 2015
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    • "Events modulated by DGKs include T-cell activation and anergy (Zha et al., 2006), synaptic vesicle fusion (McMullan et al., 2006; Yang et al., 2010), trafficking (Hasegawa et al., 2008; Los et al., 2006), and gene expression (7, 8). Further, disruption of specific DGKs has been linked to various pathologies (Fuchs et al., 2011; Leach et al., 2007; Regier et al., 2005; Rodriguez de Turco et al., 2001). It is clear, therefore, that understanding of how these enzymes are regulated is essential to understanding the regulation of the involved signaling pathways. "
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