2015
De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy
Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans M, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels R, Meisler MH, Kamsteeg EJ. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. Journal Of Medical Genetics 2015, 52: 330. PMID: 25725044, PMCID: PMC4413743, DOI: 10.1136/jmedgenet-2014-102813.Peer-Reviewed Original ResearchConceptsClinical exome sequencingClinical featuresEarly-infantile epileptic encephalopathy type 13Intellectual disabilityVoltage-gated sodium channel Nav1.6De novo SCN8A mutationFunction mutationsExome sequencingSodium channel Nav1.6Variable clinical featuresGenotype-phenotype correlationSCN8A mutationsChannel Nav1.6Hyperpolarising shiftMutant sodium channelsPatientsDe novoHeterozygous lossSodium channelsElectrophysiological analysisClinical interpretationType 13DisabilitySeizuresWildtype channel
2012
Gain-of-function Nav1.8 mutations in painful neuropathy
Faber CG, Lauria G, Merkies IS, Cheng X, Han C, Ahn HS, Persson AK, Hoeijmakers JG, Gerrits MM, Pierro T, Lombardi R, Kapetis D, Dib-Hajj SD, Waxman SG. Gain-of-function Nav1.8 mutations in painful neuropathy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 19444-19449. PMID: 23115331, PMCID: PMC3511073, DOI: 10.1073/pnas.1216080109.Peer-Reviewed Original ResearchConceptsPainful peripheral neuropathySmall fiber neuropathyPainful neuropathyPeripheral neuropathyPainful small fiber neuropathyDorsal root ganglion neuronsSodium channelsApparent underlying causePeripheral nerve axonsDRG neuronsGanglion neuronsNeuropathyNerve axonsUnderlying causeFunction variantsCurrent clampPatientsPotential pathogenicityNeuronsMutationsHyperexcitabilityAxonsResponse
1999
Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans
Bendahhou S, Cummins T, Kwiecinski H, Waxman S, Ptácek L. Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans. The Journal Of Physiology 1999, 518: 337-344. PMID: 10381583, PMCID: PMC2269438, DOI: 10.1111/j.1469-7793.1999.0337p.x.Peer-Reviewed Original ResearchConceptsChannel functionMutant channelsHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsSodium channel alpha subunitAmino acid changesSingle nucleotide substitutionKidney 293 cellsChannel alpha subunitSkeletal muscle voltage-gated sodium channelPosition 1448Sodium channel mutationsParamyotonia congenitaVoltage-gated sodium channelsSodium channel functionNucleotide substitutionsAlpha subunitSingle-strand conformation polymorphism analysisSegment S4Skeletal muscle disordersDomain IVAcid changesNew genetic mutationsDNA sequencingFast inactivation