Neural Plasticity / 2011 / Article / Tab 3

Review Article

Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders

Table 3

Selected examples of genes causing epilepsy in humans and interneuron dysfunctions in mice.



SCN1ASCN1A mutations explain the majority of Dravet syndromeClaes et al. [162]; Ohmori et al. [163]
Sugawara et al. [164]; Orrico et al. [165]
Escayg and Goldin et al. [166]
SCN1A mutations display phenotypic heterogeneity: GEFS, febrile seizures, cognitive impairmentEscayg et al. [167, 168]
Fujiwara et al. [169]; Osaka et al. [170]
Zucca et al. [171]; Orrico et al. [165]
Variants in other channels modify the phenotype of SCN1A: SCN8A Martin et al. [172]
CACNB4Ohmori et al. [173]
SCN1BSCN1B mutations cause GEFSWallace et al. [174]
ARXARX mutations cause various phenotypes including infantile spasmsShoubridge et al. [175]
CDKL5CDKL5 mutations cause early epileptic encephalopathiesKalscheuer et al. [176]; Weaving et al. 2004 [177]
Scala et al. [178]; Archer et al. [179]
Cordova-Fletes et al. [180]; Mei et al. [181]
Melani et al. [182]
MECP2MECP2 mutations explain most cases of Rett syndrome. These patients often display seizures.Amir et al. [147]; Buyse et al. [148]
GABRG2 Mutations in the gamma2 subunit of the GABAAR cause childhood absence epilepsy ± febrile seizureWallace et al. [174]; Kananura et al. [183]
Truncation of GABRG2 causes generalised epilepsy with febrile seizure (GEFS)Harkin et al. [184]
GABRA1Mutations in the alpha1 subunit of the GABAAR cause juvenile myoclonic epilepsyCossette et al. [185]
Mutations in the alpha1 subunit of the GABAAR can also cause childhood absence epilepsyMaljevic et al. [186]
CACNA1APolymorphisms associated with generalised epilepsy syndromesChioza et al. [187]
Mutations in CACNA1A can cause ataxia with generalized seizuresJouvenceau et al. [188]; Imbrici et al. [189]
CACNB4Mutations in CACNB4 cause episodic ataxia with generalized seizuresEscayg et al. [190]
CACNA1HMutations in T-type calcium channel Cav3.2 cause childhood absence epilepsyKhosravani et al. [191]
Nkx2.1Nkx2.1 haploinsufficiency leads to the “brain-lung-thyroid syndrome”Carre et al. [192]
variable phenotype: severe respiratory distress at birth, mild-moderate hypothyroidism, choreaGuillot et al. [193]
Some patients present benign hereditary chorea, occasionally with cognitive impairment and seizuresKleiner-Fisman et al. [194, 195]
Dlx5/6Dlx5/6 mutations result in craniofacial and limb anomalies: ectodermal dysplasiaMorasso et al. [196]; Lo Lacono et al. [197]
Sox 61 patient described with heterozygote Sox6 mutation: craniosynostosis and facial dysmorphisms.Tagariello et al. [198]


Scn1aScn1a (Nav1.1) expressed in most neuronal populationsYu et al. [199]
Scn1a+/−and Scn1a−/−mice develop spontaneous seizures and die prematurelyYu et al. [199]
sodium currents are specific to GABAergic interneurons in Scn1a+/− and Scn1a−/−Yu et al. [199]
Selective loss of Scn1a in interneurons recapitulates seizure disorderMartin et al. [200]
ArxRole in neuronal proliferation and migrationFricourt et al. [201, 202]
Specific requirement of Arx for interneuron migrationFriocourt and Parnavelas [203]; Poirier et al. [204]
Arx is a downstream target of Dlx1 Colasante et al. [205]
Arx(GCG)10+7 mice display seizures including spasms and no. of CB and NPY interneuronsPrice et al. [206]
Selective loss of Arx in interneurons recapitulates the seizure disorderMarsh et al. [207]
Cdkl5Cdkl5 is coexpressed with Mecp2 in cortical neurons and can phosphorylate Mecp2Mari et al. [208], Bertani et al. [209]
MecP2Mecp2 broadly represses gene expression by binding methylated CPG islandsNan et al. [210, 211]
Cacna1aCacna1atg/tg tottering mutant displays ataxia and absence seizuresNoebels et al. [212]; Fletcher et al. [213]
Gain of thalamic T-type currents cause enhanced rebound bursting of TC cells in Cacna1atg/tg, Cacna1aln/lnZhang et al. [214]; Tsakiridou et al. [215]
Interneuron selective ablation of Cacna1a leads to multiple types of generalised seizures incl. absencesRossignol et al. [63] (abstract)
Cacnb4 Cacnb4lh/lh loss-of-function mutants display spontaneous absence seizures and ataxiaBurgess et al. [216]
Thalamic tonic GABAA currents enhance rebound bursting of TC cells in Cacnb4lh/lhCope et al. [217]
Dlx1/2 Dlx1−/−Dlx2−/− mice die perinatally and display a failure of IN migration to cortex and olfactory bulbAnderson et al. [23, 218]; Bulfone et al. [219]
Dlx1−/−Dlx2+/− abnormal laminar distribution of IN and simplified morphologyCobos et al. [220]
Dlx1−/− morphological defect and postnatal loss of SST+/CR+ interneurons: spontaneous seizuresCobos et al. [221]
Nkx2.1Nkx2.1−/− die perinatally. Nkx2.1 is required for MGE interneuron generation.Sussel et al. [222]
Interneuron specific removal of Nkx2.1 results in misspecification of MGE cells into CGE cells, and seizuresButt et al. [22]
Sox6Sox6−/− dies perinatally of craniofacial anomalies
Conditional loss of Sox6 in interneurons results in misplaced/ectopic and immature basket cells (loss PV)Batista-Brito et al. [28]; Azim et al. [223]
Conditional loss of Sox6 in interneurons results in a severe epileptic encephalopathyBatista-Brito et al. [28]