title: Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice.
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.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Natalia T
authors.initials: NT
authors.lastname: Leach
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Sebastien
authors.initials: S
authors.lastname: Michaud
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: Azra H
authors.initials: AH
authors.lastname: Ligon
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Korf
authors.forename: Weining
authors.initials: W
authors.lastname: Lu
authors.forename: David J
authors.initials: DJ
authors.lastname: Harris
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Richard L
authors.initials: RL
authors.lastname: Maas
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Quade
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cole
authors.forename: Max B
authors.initials: MB
authors.lastname: Kelz
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D019852:Diacylglycerol Kinase / Q000235:genetics*; D004569:Electroencephalography; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D012640:Seizures / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C497139:DGKD protein, human; D019852:Diacylglycerol Kinase