Mutations in GABAA receptor subunits associated with genetic epilepsies

被引：192

作者：

Macdonald, Robert L. ^{[1
,2
,3
]}

Kang, Jing-Qiong ^{[1
]}

Gallagher, Martin J. ^{[1
]}

机构：

[1] Vanderbilt Univ, Dept Neurol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA

来源：

JOURNAL OF PHYSIOLOGY-LONDON | 2010年 / 588卷 / 11期

关键词：

CHILDHOOD ABSENCE EPILEPSY; FEBRILE SEIZURES PLUS; JUVENILE MYOCLONIC EPILEPSY; GENERALIZED EPILEPSY; ENDOPLASMIC-RETICULUM; SURFACE EXPRESSION; GABRG2; MUTATION; CELL-SURFACE; INHIBITION; GAMMA-2-SUBUNIT;

D O I：

10.1113/jphysiol.2010.186999

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Mutations in inhibitory GABA(A) receptor subunit genes (GABRA1, GABRB3, GABRG2 and GABRD) have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS)/severe myoclonic epilepsy in infancy (SMEI). These mutations are found in both translated and untranslated gene regions and have been shown to affect the GABA(A) receptors by altering receptor function and/or by impairing receptor biogenesis by multiple mechanisms including reducing subunit mRNA transcription or stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking.

引用

页码：1861 / 1869

页数：9

共 49 条

[11]

DELAHANTY RJ, 2010, MOL PSYCHIA IN PRESS

[12] GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies [J].

Dibbens, LM ;

Feng, HJ ;

Harkin, LA ;

Hodgson, BL ;

Scott, D ;

Jenkins, M ;

Petrou, S ;

Sutherland, GR ;

Scheffer, IE ;

Berkovic, SF ;

Macdonald, RL ;

Mulley, JC .

HUMAN MOLECULAR GENETICS, 2004, 13 (13) :1315-1319

[13] GABAA receptor γ2 subunit mutations linked to human epileptic syndromes differentially affect phasic and tonic inhibition [J].

Eugene, Emmanuel ;

Depienne, Christel ;

Baulac, Stephanie ;

Baulac, Michel ;

Fritschy, Jean Marc ;

Le Guern, Eric ;

Miles, Richard ;

Poncer, Jean Christophe .

JOURNAL OF NEUROSCIENCE, 2007, 27 (51) :14108-14116

[14] Intracortical hyperexcitability in humans with a GABAA receptor mutation [J].

Fedi, Marco ;

Berkovic, Samuel F. ;

Macdonell, Richard A. L. ;

Curatolo, Josie M. ;

Marini, Carla ;

Reutens, David C. .

CEREBRAL CORTEX, 2008, 18 (03) :664-669

[15] A GABAA receptor mutation causing generalized epilepsy reduces benzodiazepine receptor binding [J].

Fedi, Marco ;

Berkovic, Samuel F. ;

Marini, Carla ;

Mulligan, Rachel ;

Tochon-Danguy, Henri ;

Reutens, David C. .

NEUROIMAGE, 2006, 32 (03) :995-1000

[16] δ subunit susceptibility variants E177A and R220H associated with complex epilepsy alter channel gating and surface expression of α4β2δ GABAA receptors [J].

Feng, HJ ;

Kang, JQ ;

Song, LY ;

Dibbens, L ;

Mulley, J ;

Macdonald, RL .

JOURNAL OF NEUROSCIENCE, 2006, 26 (05) :1499-1506

[17] A mutation in the GABAA receptor α1 subunit linked to human epilepsy affects channel gating properties [J].

Fisher, JL .

NEUROPHARMACOLOGY, 2004, 46 (05) :629-637

[18] A γ2(R43Q) mutation, linked to epilepsy in humans, alters GABAA receptor assembly and modifies subunit composition on the cell surface [J].

Frugier, Guillaume ;

Coussen, Francoise ;

Giraud, Marie-France ;

Odessa, Marie-Francoise ;

Emerit, Michel B. ;

Boue-Grabot, Eric ;

Garret, Maurice .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (06) :3819-3828

[19] The GABAA receptor α1 subunit epilepsy mutation A322D inhibits transmembrane helix formation and causes proteasomal degradation [J].

Gallagher, Martin J. ;

Ding, Li ;

Maheshwari, Ankit ;

Macdonald, Robert L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (32) :12999-13004

[20] Endoplasmic reticulum retention and associated degradation of a GABAA receptor epilepsy mutation that inserts an aspartate in the M3 transmembrane segment of the α1 subunit [J].

Gallagher, MJ ;

Shen, WZ ;

Song, LY ;

Macdonald, RL .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (45) :37995-38004

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