Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice

Natalia T Leach; Yi Sun; Sebastien Michaud; Yi Zheng; Keith L Ligon; Azra H Ligon; Thomas Sander; Bruce R Korf; Weining Lu; David J Harris; James F Gusella; Richard L Maas; Bradley J Quade; Andrew J Cole; Max B Kelz; Cynthia C Morton

doi:10.1086/513019

Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice

Natalia T Leach, Yi Sun, Sebastien Michaud, Yi Zheng, Keith L Ligon, Azra H Ligon, Thomas Sander, Bruce R Korf, Weining Lu, David J Harris, James F Gusella, Richard L Maas, Bradley J Quade, Andrew J Cole, Max B Kelz, Cynthia C Morton

Division of Evolution, Infection and Genomics

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	792-9
Number of pages	8
Journal	American Journal of Human Genetics
Volume	80
Issue number	4
DOIs	https://doi.org/10.1086/513019
Publication status	Published - Apr 2007

Keywords

Abnormalities, Multiple
Animals
Chromosome Mapping
Chromosomes, Human, Pair 2
Diacylglycerol Kinase
Electroencephalography
Female
Genetic Predisposition to Disease
Humans
In Situ Hybridization, Fluorescence
Mice
Seizures
Translocation, Genetic
Comparative Study
Journal Article
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/513019

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Leach, N. T., Sun, Y., Michaud, S., Zheng, Y., Ligon, K. L., Ligon, A. H., Sander, T., Korf, B. R., Lu, W., Harris, D. J., Gusella, J. F., Maas, R. L., Quade, B. J., Cole, A. J., Kelz, M. B., & Morton, C. C. (2007). Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice. American Journal of Human Genetics, 80(4), 792-9. https://doi.org/10.1086/513019

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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.",

keywords = "Abnormalities, Multiple, Animals, Chromosome Mapping, Chromosomes, Human, Pair 2, Diacylglycerol Kinase, Electroencephalography, Female, Genetic Predisposition to Disease, Humans, In Situ Hybridization, Fluorescence, Mice, Seizures, Translocation, Genetic, Comparative Study, Journal Article, Research Support, N.I.H., Extramural",

author = "Leach, {Natalia T} and Yi Sun and Sebastien Michaud and Yi Zheng and Ligon, {Keith L} and Ligon, {Azra H} and Thomas Sander and Korf, {Bruce R} and Weining Lu and Harris, {David J} and Gusella, {James F} and Maas, {Richard L} and Quade, {Bradley J} and Cole, {Andrew J} and Kelz, {Max B} and Morton, {Cynthia C}",

year = "2007",

month = apr,

doi = "10.1086/513019",

language = "English",

volume = "80",

pages = "792--9",

journal = "American Journal of Human Genetics",

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T1 - Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice

AU - Leach, Natalia T

AU - Sun, Yi

AU - Michaud, Sebastien

AU - Zheng, Yi

AU - Ligon, Keith L

AU - Ligon, Azra H

AU - Sander, Thomas

AU - Korf, Bruce R

AU - Lu, Weining

AU - Harris, David J

AU - Gusella, James F

AU - Maas, Richard L

AU - Quade, Bradley J

AU - Cole, Andrew J

AU - Kelz, Max B

AU - Morton, Cynthia C

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Abnormalities, Multiple

KW - Animals

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 2

KW - Diacylglycerol Kinase

KW - Electroencephalography

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Mice

KW - Seizures

KW - Translocation, Genetic

KW - Comparative Study

KW - Journal Article

KW - Research Support, N.I.H., Extramural

U2 - 10.1086/513019

DO - 10.1086/513019

M3 - Article

C2 - 17357084

SN - 0002-9297

VL - 80

SP - 792

EP - 799

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 4

ER -

Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice

Abstract

Keywords

UN SDGs

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