2017
COL6A5 variants in familial neuropathic chronic itch
Martinelli-Boneschi F, Colombi M, Castori M, Devigili G, Eleopra R, Malik RA, Ritelli M, Zoppi N, Dordoni C, Sorosina M, Grammatico P, Fadavi H, Gerrits MM, Almomani R, Faber CG, Merkies IS, Toniolo D, Network F, Cocca M, Doglioni C, Waxman S, Dib-Hajj S, Taiana M, Sassone J, Lombardi R, Cazzato D, Zauli A, Santoro S, Marchi M, Lauria G. COL6A5 variants in familial neuropathic chronic itch. Brain 2017, 140: 555-567. PMID: 28073787, DOI: 10.1093/brain/aww343.Peer-Reviewed Original ResearchMeSH KeywordsAdultCollagen Type VIDNA Mutational AnalysisFamily HealthFemaleGenetic VariationHumansMaleMiddle AgedPeripheral Nervous System DiseasesPruritusSkinConceptsChronic itchSmall fiber neuropathyJHS/EDS-HT patientsJoint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility typeNew candidate therapeutic targetsIntraepidermal nerve fiber densityEhlers-Danlos syndrome hypermobility typeEDS-HT patientsNonsense variantNerve fiber densitySkin of patientsCandidate therapeutic targetUnrelated sporadic patientsWhole-exome sequencingItch reliefNeuropathic itchDiabetic patientsHypermobility typeSomatosensory pathwaysHealthy controlsSkin biopsiesSide effectsTherapeutic targetPatientsSporadic patients
2016
Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling
Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hajj SD, Waxman SG. Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling. JAMA Neurology 2016, 73: 659. PMID: 27088781, DOI: 10.1001/jamaneurol.2016.0389.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdultAnalgesics, Non-NarcoticBrainCarbamazepineChronic PainDNA Mutational AnalysisDouble-Blind MethodElectric StimulationErythromelalgiaFemaleGanglia, SpinalHumansMagnetic Resonance ImagingMaleMutationNAV1.7 Voltage-Gated Sodium ChannelPain MeasurementRegression AnalysisSensory Receptor CellsConceptsMean episode durationDRG neuronsPatient 1Nav1.7 mutationEpisode durationDorsal root ganglion neuronsPlacebo-controlled studyMaintenance periodAttenuation of painEffects of carbamazepineBrain activityFunctional magnetic resonance imagingMagnetic resonance imagingT mutationMutant channelsFunctional magnetic resonanceNeuropathic painSecondary somatosensoryChronic painPain areaPatient 2Ganglion neuronsEffective pharmacotherapyNight awakeningsPlacebo
2014
Paroxysmal itch caused by gain-of-function Nav1.7 mutation
Devigili G, Eleopra R, Pierro T, Lombardi R, Rinaldo S, Lettieri C, Faber C, Merkies I, Waxman S, Lauria G. Paroxysmal itch caused by gain-of-function Nav1.7 mutation. Pain 2014, 155: 1702-1707. PMID: 24820863, DOI: 10.1016/j.pain.2014.05.006.Peer-Reviewed Original ResearchConceptsIntraepidermal nerve fiber densityNerve fiber densityFiber densityAutonomic cardiovascular reflexesFunction Nav1.7 mutationsNerve conduction studiesManifestations of allergyQuantitative sensory testingParadoxical heat sensationProfile assessmentConsequence of diseaseNav1.7 sodium channelCardiovascular reflexesPregabalin treatmentAutonomic testsConduction studiesNav1.7 mutationPain thresholdClinical pictureSystemic diseaseSomatosensory pathwaysSkin biopsiesIndex patientsSensory testingSpicy foods
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
Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation
Bendahhou S, Cummins T, Tawil R, Waxman S, Ptácek L. Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation. Journal Of Neuroscience 1999, 19: 4762-4771. PMID: 10366610, PMCID: PMC6782655, DOI: 10.1523/jneurosci.19-12-04762.1999.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedDNA Mutational AnalysisDNA PrimersGene ExpressionHumansHyperkalemiaIon Channel GatingKidneyKineticsMaleMiddle AgedMolecular Sequence DataNAV1.4 Voltage-Gated Sodium ChannelParalyses, Familial PeriodicPatch-Clamp TechniquesPoint MutationProtein Structure, TertiarySequence Homology, Amino AcidSodium ChannelsTransfectionConceptsSegments S5Point mutationsS5 segmentVoltage-Gated Sodium ChannelSodium channelsTransmembrane segments S5Cytoplasmic interfaceWild-type channelsParalysis phenotypeHomologous domainsVoltage-sensitive sodium channelsPotassium-aggravated myotoniaNew point mutationPhenylalanine substitutionSkeletal muscle disordersHyperkalaemic periodic paralysisFast inactivationSecond domainMutationsGenesChannel deactivationInactivationChannel activationSlow inactivationT704M mutation