0000000000512355

AUTHOR

Lynne A. Wolfe

showing 2 related works from this author

Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.

2014

The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemica…

Models MolecularInterferon-Induced Helicase IFIH1Molecular Sequence DataHDE NEU PEDElectrophoretic Mobility Shift AssayBiologymedicine.disease_causeNervous System MalformationsReal-Time Polymerase Chain ReactionArticleDEAD-box RNA HelicasesImmune systemAutoimmune Diseases of the Nervous SystemDownregulation and upregulationAnalysis of Variance; Autoimmune Diseases of the Nervous System; Base Sequence; DEAD-box RNA Helicases; Electrophoretic Mobility Shift Assay; Exome; HEK293 Cells; Humans; Interferon Type I; Microsatellite Repeats; Molecular Sequence Data; Mutation; Nervous System Malformations; Real-Time Polymerase Chain Reaction; Sequence Analysis DNA; Signal Transduction; Spectrum Analysis; Models Molecular; Phenotype; GeneticsModelsInterferonGeneticsmedicineHumansExomeMutationAnalysis of VarianceBase SequenceSpectrum AnalysisMolecularRNAMDA5DNASequence Analysis DNAMolecular biology3. Good healthInterferon Tipo IHEK293 CellsPhenotypeInterferon Type IMutationCancer researchSignal transductionSequence AnalysisInterferon type Imedicine.drugMicrosatellite RepeatsSignal TransductionNature genetics
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Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes

2015

Contains fulltext : 153827.pdf (Publisher’s version ) (Open Access) Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based s…

Models MolecularCandidate geneHirsutismProtein ConformationHeLa Cellmedicine.disease_causeTranscriptomeTwist transcription factorModelsGenetics(clinical)ExomeEye AbnormalitiesNon-U.S. Gov'tExomeGenetics (clinical)ZebrafishGeneticsMutationMicroscopyMacrostomiaSetleis syndromeHypertelorismResearch Support Non-U.S. Gov'tHypertrichosiEyelid DiseaseGENÉTICAPhenotypeEyelid DiseasesAbnormalitiesMultipleSequence AnalysisHumanChromatin ImmunoprecipitationMolecular Sequence DataMutation MissenseHypertrichosisAbnormalities; Multiple; Amino Acid Sequence; Animals; Base Sequence; Chromatin Immunoprecipitation; Exome; Eye Abnormalities; Eyelid Diseases; HeLa Cells; Hirsutism; Humans; Hypertelorism; Hypertrichosis; Macrostomia; Microscopy; Electron; Molecular Sequence Data; Mutation; Missense; Protein Conformation; Repressor Proteins; Sequence Analysis; DNA; Skin Abnormalities; Twist Transcription Factor; Zebrafish; Models; Molecular; Phenotype; Genetics; Genetics (clinical)Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0]BiologyResearch SupportElectronArticleFrameshift mutationGeneticAblepharon macrostomia syndromeSkin AbnormalitieGeneticsmedicineJournal ArticleAnimalsHumansAbnormalities MultipleAmino Acid SequenceNeurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]Base SequenceAnimalTwist-Related Protein 1MolecularSequence Analysis DNADNARepressor Proteinmedicine.diseaseRepressor ProteinsTwist Transcription FactorEye AbnormalitieMicroscopy ElectronMutationSkin Abnormalitiessense organsMissenseNanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]HeLa CellsAmerican journal of human genetics
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