2015
Gene expression profiling in pachyonychia congenita skin
Cao YA, Hickerson RP, Seegmiller BL, Grapov D, Gross MM, Bessette MR, Phinney BS, Flores MA, Speaker TJ, Vermeulen A, Bravo AA, Bruckner AL, Milstone LM, Schwartz ME, Rice RH, Kaspar RL. Gene expression profiling in pachyonychia congenita skin. Journal Of Dermatological Science 2015, 77: 156-165. PMID: 25656049, PMCID: PMC4374015, DOI: 10.1016/j.jdermsci.2015.01.001.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaTape-strip samplesPlantar skinSerine protease inhibitorNon-PC controlsPainful plantar keratodermaSkin barrier homeostasisPC patientsPatient groupControl volunteersMajor symptomsSkin biopsiesPC pathogenesisPlantar keratodermaPathogenic sequelaeSkin disordersBarrier homeostasisPatient samplesGene expression profilingKeratinocyte proliferationEnvelope proteinBiopsyMRNA analysisProtease inhibitorsSkin
2014
The molecular genetic analysis of the expanding pachyonychia congenita case collection
Wilson N, O'Toole E, Milstone L, Hansen C, Shepherd A, Al‐Asadi E, Schwartz M, McLean W, Sprecher E, Smith F. The molecular genetic analysis of the expanding pachyonychia congenita case collection. British Journal Of Dermatology 2014, 171: 343-355. PMID: 24611874, PMCID: PMC4282083, DOI: 10.1111/bjd.12958.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaInternational Pachyonychia Congenita Research RegistryClinical diagnosisPeripheral blood leucocytesFollicular keratosisResearch RegistryBlood leucocytesOral leucokeratosisNail dystrophyKeratin mutationsUnreported mutationsPalmoplantar keratodermaChain reaction productsCase collectionDiagnosisKRT6CKRT6APolymerase chain reaction productsMolecular genetic analysisKRT6BKRT16KRT17Keratin genesMutationsTotal numberReport of the 10th Annual International Pachyonychia Congenita Consortium Meeting
van Steensel MAM, Coulombe PA, Kaspar RL, Milstone LM, McLean IWH, Roop DR, Smith FJD, Sprecher E, Schwartz ME. Report of the 10th Annual International Pachyonychia Congenita Consortium Meeting. Journal Of Investigative Dermatology 2014, 134: 588-591. PMID: 24518109, PMCID: PMC3930927, DOI: 10.1038/jid.2013.392.Commentaries, Editorials and Letters
2011
An appraisal of oral retinoids in the treatment of pachyonychia congenita
Gruber R, Edlinger M, Kaspar RL, Hansen CD, Leachman S, Milstone LM, Smith FJ, Sidoroff A, Fritsch PO, Schmuth M. An appraisal of oral retinoids in the treatment of pachyonychia congenita. Journal Of The American Academy Of Dermatology 2011, 66: e193-e199. PMID: 21601946, DOI: 10.1016/j.jaad.2011.02.003.Peer-Reviewed Original ResearchConceptsOral retinoidsOral retinoid treatmentPachyonychia congenitaAdverse effectsRetinoid treatmentVisual analog pain scaleSatisfaction scoresCareful dose titrationPainful plantar keratodermaAnalog pain scaleRetrospective cross-sectional surveyCross-sectional study designOverall satisfaction scoreRisk/benefit analysisCross-sectional surveyPotential adverse effectsPlantar painDose titrationPain scalePain changeClinical scoresNail changesPatient's perspectivePlantar keratodermaNail dystrophyA Large Mutational Study in Pachyonychia Congenita
Wilson NJ, Leachman SA, Hansen CD, McMullan AC, Milstone LM, Schwartz ME, McLean WH, Hull PR, Smith FJ. A Large Mutational Study in Pachyonychia Congenita. Journal Of Investigative Dermatology 2011, 131: 1018-1024. PMID: 21326300, DOI: 10.1038/jid.2011.20.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaFrame insertion/deletion mutationsPainful palmoplantar keratodermaAdditional clinical featuresHeterozygous splice site mutationClinical featuresFollicular keratosisRare autosomal dominant skin disorderOral leukokeratosisNail dystrophyAutosomal dominant skin disorderSkin disordersHeterozygous missenseClinical diagnosisHeterozygous mutationsDominant skin disorderHotspot codonsPalmoplantar keratodermaKRT6AKRT16KRT17Splice site mutationKRT6BCongenitaPersonalized medicine
2010
Development of Quantitative Molecular Clinical End Points for siRNA Clinical Trials
Hickerson RP, Leachman SA, Pho LN, Gonzalez-Gonzalez E, Smith FJ, McLean WH, Contag CH, Leake D, Milstone LM, Kaspar RL. Development of Quantitative Molecular Clinical End Points for siRNA Clinical Trials. Journal Of Investigative Dermatology 2010, 131: 1029-1036. PMID: 21191405, DOI: 10.1038/jid.2010.372.Peer-Reviewed Original ResearchConceptsClinical trialsPachyonychia congenitaEnd pointPhase 1b clinical trialClinical end pointsRare skin disorderMolecular end pointsTypes of trialsImmune surveillancePatient-derived keratinocytesSkin disordersSustained inhibitionTreatment resultsRNAi-based therapeuticsRNA interferenceMRNA levelsTrialsTotal RNAHuman skinKeratinocyte culturesMRNAAmplifiable mRNATherapeuticsInhibitorsInhibition
2009
First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder
Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM, Hansen CD, Eliason MJ, Srivatsa GS, Kornbrust DJ, Smith FJ, McLean WI, Milstone LM, Kaspar RL. First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder. Molecular Therapy 2009, 18: 442-446. PMID: 19935778, PMCID: PMC2839285, DOI: 10.1038/mt.2009.273.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaPhase Ib clinical trialSubjective patient assessmentPhase Ib trialDose-escalation trialClinical efficacy measuresAutosomal dominant syndromeIb trialAdverse eventsWashout periodPatient assessmentEfficacy measuresPlantar callusClinical trialsPlantar keratodermaOpposite footSkin disordersSkin diseasesClinical settingDominant syndromeSatisfactory treatmentAdditional studiesTrialsGenetic disordersSiRNA
2008
Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita
Leachman SA, Hickerson RP, Hull PR, Smith FJ, Milstone LM, Lane EB, Bale SJ, Roop DR, McLean WH, Kaspar RL. Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita. Journal Of Dermatological Science 2008, 51: 151-157. PMID: 18495438, PMCID: PMC2587483, DOI: 10.1016/j.jdermsci.2008.04.003.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaQuantitative RT-PCRRT-PCRReal-time RT-PCRQuantitative real-time RT-PCRClinical efficacyGenetic skin disordersClinical trialsCandidate siRNASkin disordersRNA interferenceNovel therapeuticsPotent inhibitionTherapeutic siRNAsClinical applicationDisordersGenetic disordersPhysiciansCongenitaMutant allelesSiRNAHuman diseasesKeratin disordersPatientsDisease
2007
Single-Nucleotide-Specific siRNA Targeting in a Dominant-Negative Skin Model
Hickerson RP, Smith FJ, Reeves RE, Contag CH, Leake D, Leachman SA, Milstone LM, McLean WH, Kaspar RL. Single-Nucleotide-Specific siRNA Targeting in a Dominant-Negative Skin Model. Journal Of Investigative Dermatology 2007, 128: 594-605. PMID: 17914454, DOI: 10.1038/sj.jid.5701060.Peer-Reviewed Original ResearchConceptsWild-type gene expressionBicistronic reporter constructFilament formationDominant-negative genetic disordersNumerous genetic disordersGenetic disordersKeratin filament formationRNA interferenceMutant formsReporter constructsGene expressionMutant mRNAFluorescent reportersMutant allelesCell culture modelSiRNAsSimultaneous expressionK6aK mutationPachyonychia congenitaExpressionCulture modelHuman keratinocytesSiRNASelective inhibition
2005
Treatment of Pachyonychia Congenita
Milstone LM, Fleckman P, Leachman SA, Leigh IM, Paller AS, van Steensel MA, Swartling C. Treatment of Pachyonychia Congenita. Journal Of Investigative Dermatology Symposium Proceedings 2005, 10: 18-20. PMID: 16250205, DOI: 10.1111/j.1087-0024.2005.10203.x.Peer-Reviewed Original ResearchClinical and Pathological Features of Pachyonychia Congenita
Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, Lunny DP, Milstone LM, van Steensel MA, Munro CS, O'Toole EA, Celebi JT, Kansky A, Lane E. Clinical and Pathological Features of Pachyonychia Congenita. Journal Of Investigative Dermatology Symposium Proceedings 2005, 10: 3-17. PMID: 16250204, DOI: 10.1111/j.1087-0024.2005.10202.x.Peer-Reviewed Original ResearchConceptsPachyonychia congenitaPainful plantar keratodermaUnreported clinical featuresVariable clinical findingsPossible pathogenic mechanismsEarly primary tooth lossPrimary tooth lossNipple lesionsPC patientsAmbulatory aidsNatal teethClinical featuresClinical findingsFollicular keratosisLaryngeal involvementProspective evaluationPathological featuresTooth lossPalmar keratodermaOral mucosaResearch RegistryOral leukokeratosisPlantar keratodermaPathogenic mechanismsCutaneous cysts