2023
De novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis
Timberlake A, McGee S, Allington G, Kiziltug E, Wolfe E, Stiegler A, Boggon T, Sanyoura M, Morrow M, Wenger T, Fernandes E, Caluseriu O, Persing J, Jin S, Lifton R, Kahle K, Kruszka P. De novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis. American Journal Of Human Genetics 2023, 110: 846-862. PMID: 37086723, PMCID: PMC10183468, DOI: 10.1016/j.ajhg.2023.03.017.Peer-Reviewed Original ResearchConceptsDamaging de novo variantsChromatin modificationsDe novo variantsCranial neural crest cellsGenome-wide significanceNeural crest cellsNovo variantsRetinoic acid receptor alphaExome sequence dataAcid receptor alphaTranscriptional regulationProband-parent triosGene transcriptionSequence dataCrest cellsOsteoblast differentiationCS phenotypeMendelian formsRecurrent gainsGenesRisk genesGenetic etiologyRetinoic acidReceptor alphaNeurodevelopmental disordersQuantifying the Impact of Genetics on Neurocognition in Nonsyndromic Sagittal Craniosynostosis
Junn A, Dinis J, Long A, Timberlake A, Persing J, Alperovich M. Quantifying the Impact of Genetics on Neurocognition in Nonsyndromic Sagittal Craniosynostosis. Plastic & Reconstructive Surgery 2023, 152: 300e-306e. PMID: 36912936, DOI: 10.1097/prs.0000000000010400.Peer-Reviewed Original ResearchConceptsFull-scale intelligence quotientHigh-risk mutationsNonsyndromic craniosynostosisNeurocognitive outcomesDouble-blinded cohort studySignificant differencesCLINICAL QUESTION/LEVELVisuomotor integrationTime of surgeryType of surgeryHigh-risk genotypesPoor neurocognitive outcomesNonsyndromic sagittal craniosynostosisHigh-risk genesPresence of mutationsCohort studySurgery typePatient factorsNeurodevelopmental delayAnalysis of covarianceNeurocognitive testingNeurocognitive effectsPatientsSociodemographic factorsSagittal craniosynostosis
2022
De novo mutations in the BMP signaling pathway in lambdoid craniosynostosis
Timberlake AT, Kiziltug E, Jin SC, Nelson-Williams C, Loring E, Allocco A, Marlier A, Banka S, Stuart H, Passos-Buenos M, Rosa R, Rogatto S, Tonne E, Stiegler A, Boggon T, Alperovich M, Steinbacher D, Staffenberg D, Flores R, Persing J, Kahle K, Lifton R. De novo mutations in the BMP signaling pathway in lambdoid craniosynostosis. Human Genetics 2022, 142: 21-32. PMID: 35997807, DOI: 10.1007/s00439-022-02477-2.Peer-Reviewed Original ResearchConceptsDe novo mutationsDamaging de novo mutationsSingle-cell RNA sequencing analysisTranscriptional co-repressorTarget sequence recognitionRNA sequencing analysisTranscription factor NfixNovo mutationsEnrichment of mutationsBMP receptorsCo-repressorParent-offspring triosTranscription factorsGenetic gainImplicating perturbationsOsteoblast precursorsPremature suture fusionSequencing analysisMolecular etiologySequence recognitionMissense mutationsMutationsExome sequencingGenetic etiologyOsteoprogenitor cells
2019
Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis
Timberlake AT, Jin SC, Nelson-Williams C, Wu R, Furey CG, Islam B, Haider S, Loring E, Galm A, Steinbacher D, Larysz D, Staffenberg D, Flores R, Rodriguez E, Boggon T, Persing J, Lifton R, Lifton RP, Gunel M, Mane S, Bilguvar K, Gerstein M, Loring E, Nelson-Williams C, Lopez F, Knight J. Mutations in TFAP2B and previously unimplicated genes of the BMP, Wnt, and Hedgehog pathways in syndromic craniosynostosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 15116-15121. PMID: 31292255, PMCID: PMC6660739, DOI: 10.1073/pnas.1902041116.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlpha CateninChildChild, PreschoolCraniosynostosesExomeExome SequencingFemaleGene ExpressionGlypicansHistone AcetyltransferasesHumansMaleMutationNuclear ProteinsPedigreeRisk AssessmentSignal TransductionSkullSOXC Transcription FactorsTranscription Factor AP-2Zinc Finger Protein Gli2ConceptsRare damaging mutationsSyndromic craniosynostosisCongenital anomaliesDamaging mutationsSyndromic casesExome sequencingAdditional congenital anomaliesFrequent congenital anomaliesDamaging de novo mutationsNeural crest cell migrationDamaging de novoCrest cell migrationCS patientsMutation burdenChromatin modifiersSubsequent childrenTranscription factorsDe novo mutationsCS casesCS geneHedgehog pathwayDisease locusPremature fusionFunction mutationsCraniosynostosis
2017
De novo mutations in inhibitors of Wnt, BMP, and Ras/ERK signaling pathways in non-syndromic midline craniosynostosis
Timberlake AT, Furey CG, Choi J, Nelson-Williams C, Loring E, Galm A, Kahle K, Steinbacher D, Larysz D, Persing J, Lifton R, Bilguvar K, Mane S, Tikhonova I, Castaldi C, Knight J. De novo mutations in inhibitors of Wnt, BMP, and Ras/ERK signaling pathways in non-syndromic midline craniosynostosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e7341-e7347. PMID: 28808027, PMCID: PMC5584457, DOI: 10.1073/pnas.1709255114.Peer-Reviewed Original ResearchConceptsBone morphogenetic proteinRas/ERKDe novo mutationsNovo mutationsRas/ERK pathwayDamaging de novo mutationsHigh locus heterogeneityRare syndromic diseaseCommon risk variantsInhibitor of WntSyndromic craniosynostosesNew genesParent-offspring triosSyndromic diseaseMorphogenetic proteinsNegative regulatorERK pathwayMore cranial suturesGenesMidline craniosynostosisRisk variantsWntLocus heterogeneityMutationsExome sequencing
1996
Frequent clones of p53-mutated keratinocytes in normal human skin
Jonason A, Kunala S, Price G, Restifo R, Spinelli H, Persing J, Leffell D, Tarone R, Brash D. Frequent clones of p53-mutated keratinocytes in normal human skin. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 14025-14029. PMID: 8943054, PMCID: PMC19488, DOI: 10.1073/pnas.93.24.14025.Peer-Reviewed Original ResearchConceptsP53-mutated keratinocytesNormal individualsSun-shielded skinSun-exposed skinNormal human skinHuman skinWhole-mount preparationsP53-mutated cellsCancer predictsDermal-epidermal junctionSubstantial burdenFrequent clonesClonal expansionHair folliclesGenetic hitsTumor promoterSkinKeratinocytesCells