2020
Whole-Exome Sequencing in 97 Families with Renal Ciliopathies Reveals a Causative Mutation in a Known Kidney Disease Gene in 62% and Identifies Potential Novel Causative Genes
Deutsch K, Klambt V, Kitzler T, Jobst-Schwan T, Shril S, Mane S, Hildebrandt F. Whole-Exome Sequencing in 97 Families with Renal Ciliopathies Reveals a Causative Mutation in a Known Kidney Disease Gene in 62% and Identifies Potential Novel Causative Genes. Journal Of The American Society Of Nephrology 2020, 31: 487-487. DOI: 10.1681/asn.20203110s1487b.Peer-Reviewed Original Research
2018
GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome
Hermle T, Schneider R, Schapiro D, Braun DA, van der Ven AT, Warejko JK, Daga A, Widmeier E, Nakayama M, Jobst-Schwan T, Majmundar AJ, Ashraf S, Rao J, Finn LS, Tasic V, Hernandez JD, Bagga A, Jalalah SM, El Desoky S, Kari JA, Laricchia KM, Lek M, Rehm HL, MacArthur DG, Mane S, Lifton RP, Shril S, Hildebrandt F. GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. Journal Of The American Society Of Nephrology 2018, 29: 2123-2138. PMID: 29959197, PMCID: PMC6065084, DOI: 10.1681/asn.2017121312.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementCells, CulturedCohort StudiesDisease ProgressionDrosophila melanogasterExome SequencingFemaleGene Expression RegulationGenetic Predisposition to DiseaseHumansMaleMass ScreeningMembrane ProteinsMutation, MissenseNephrotic SyndromePedigreePhosphate-Binding ProteinsPodocytesRab5 GTP-Binding ProteinsReal-Time Polymerase Chain ReactionRenal Insufficiency, ChronicRNA, Small InterferingConceptsSteroid-resistant nephrotic syndromeNovel monogenic causesCoimmunoprecipitation assaysHomozygous missense mutationPatient-derived mutationsMissense mutationsMonogenic causesHEK293T cellsActive Rab5GAPVD1Nephrotic syndromePodocyte migration rateEctopic expressionCases of SRNSPartial colocalizationSpecific pathogenetic pathwaysWhole-exome sequencingEarly-onset NSHuman NFunctional significancePodocyte migrationProteinMutationsPhysical interactionRab5Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment
Ashraf S, Kudo H, Rao J, Kikuchi A, Widmeier E, Lawson JA, Tan W, Hermle T, Warejko JK, Shril S, Airik M, Jobst-Schwan T, Lovric S, Braun DA, Gee HY, Schapiro D, Majmundar AJ, Sadowski CE, Pabst WL, Daga A, van der Ven AT, Schmidt JM, Low BC, Gupta AB, Tripathi BK, Wong J, Campbell K, Metcalfe K, Schanze D, Niihori T, Kaito H, Nozu K, Tsukaguchi H, Tanaka R, Hamahira K, Kobayashi Y, Takizawa T, Funayama R, Nakayama K, Aoki Y, Kumagai N, Iijima K, Fehrenbach H, Kari JA, El Desoky S, Jalalah S, Bogdanovic R, Stajić N, Zappel H, Rakhmetova A, Wassmer SR, Jungraithmayr T, Strehlau J, Kumar AS, Bagga A, Soliman NA, Mane SM, Kaufman L, Lowy DR, Jairajpuri MA, Lifton RP, Pei Y, Zenker M, Kure S, Hildebrandt F. Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nature Communications 2018, 9: 1960. PMID: 29773874, PMCID: PMC5958119, DOI: 10.1038/s41467-018-04193-w.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsChildChild, PreschoolDisease Models, AnimalDNA Mutational AnalysisDrug ResistanceExome SequencingFemaleGene Knockdown TechniquesGlucocorticoidsHEK293 CellsHigh-Throughput Nucleotide SequencingHumansInfantMaleMiceMice, Inbred C57BLMice, KnockoutMiddle AgedMutationNephrotic SyndromePedigreePodocytesProtein Interaction MapsRhoA GTP-Binding ProteinRNA, Small InterferingTreatment OutcomeConceptsKnockdown of DLC1Small GTPase activityExchange factorNephrotic syndromeRhoA regulationGTPase activityDifferent genesDLC1GenesNS phenotypePotential therapeutic targetChronic kidney diseaseMutationsCultured podocytesKnockdownTherapeutic targetMigration rateSteroid treatmentKidney diseaseKnockout micePathogenic pathwaysFrequent causeITSN1Cdc42ITSN2A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux
van der Ven AT, Kobbe B, Kohl S, Shril S, Pogoda HM, Imhof T, Ityel H, Vivante A, Chen J, Hwang DY, Connaughton DM, Mann N, Widmeier E, Taglienti M, Schmidt JM, Nakayama M, Senguttuvan P, Kumar S, Tasic V, Kehinde EO, Mane SM, Lifton RP, Soliman N, Lu W, Bauer SB, Hammerschmidt M, Wagener R, Hildebrandt F. A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux. PLOS ONE 2018, 13: e0191224. PMID: 29351342, PMCID: PMC5774751, DOI: 10.1371/journal.pone.0191224.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAnimals, NewbornBiomarkers, TumorCalcium-Binding ProteinsChildConsanguinityConserved SequenceExonsExtracellular Matrix ProteinsFraser SyndromeGene Expression Regulation, DevelopmentalHomozygoteHumansMaleMiceModels, AnimalModels, MolecularMutation, MissensePedigreeSequence Homology, Amino AcidUrogenital AbnormalitiesUrogenital SystemVesico-Ureteral RefluxConceptsMetanephric mesenchymeUreteric budWhole-exome sequencingHomozygosity mappingIntermolecular disulfide bond formationDisulfide bond formationDirect interactorsNeomorphic effectMonogenic causesCysteine residuesHomozygous missense mutationComplex subunit 1Unpaired cysteine residueNovel CAKUTSubunit 1Homozygous missense variantFraser ComplexMissense mutationsGenesProteinInteractorsMissense variantsMutationsExome sequencingNephrogenic zone
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
2015
Mutation in <i>GM2A</i> Leads to a Progressive Chorea-dementia Syndrome
Salih M, Seidahmed M, Khashab H, Hamad M, Bosley T, Burn S, Myers A, Landsverk M, Crotwell P, Bilguvar K, Mane S, Kruer M. Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome. Tremor And Other Hyperkinetic Movements 2015, 5: 306. DOI: 10.5334/tohm.246.Peer-Reviewed Original ResearchMacular cherry-red spotsChildhood-onset choreaCherry-red spotWhole-exome sequencingMacular findingsProgressive choreaIntractable seizuresHomozygous missense mutationNeurodegenerative courseProfound hypotoniaRare formVolitional movementPhenotypic spectrumChoreaExome sequencingGM2 gangliosidosisHyperacusisPatientsSaudi familyNeurodegenerative disease genesMissense mutationsGangliosidosisHomozygosity mappingVariant phenotypesMutations
1990
Quantitation of the ras gene product in leukemic blast cells using enzymatic staining.
Gutheil J, Mane S, Bass K, Lee E, Needleman S. Quantitation of the ras gene product in leukemic blast cells using enzymatic staining. BioTechniques 1990, 9: 212-7. PMID: 2205250.Peer-Reviewed Original ResearchConceptsRas gene productGene productsRas speciesRas protein levelsProtein of interestGene product levelsQuantitation of proteinsSpecific ras mutationsUse of electrophoresisProtein levelsRas mutationsProteinP21 expressionHuman malignanciesSpeciesCellsLeukemic cellsMutationsEnzymatic stainingHigh specificityRadioactive reagentsExpressionElectrophoresisAssaysVivoRAS gene activation in acute myelogenous leukemia: Analysis by in vitro amplification and dna base sequence determination
Mane S, Meltzer S, Gutheil J, Kapil V, Lee E, Needleman S. RAS gene activation in acute myelogenous leukemia: Analysis by in vitro amplification and dna base sequence determination. Genes Chromosomes And Cancer 1990, 2: 71-77. PMID: 2278967, DOI: 10.1002/gcc.2870020113.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCohort StudiesDNA Mutational AnalysisDNA, NeoplasmExonsGene Expression Regulation, NeoplasticGenes, rasHumansIatrogenic DiseaseLeukemia, Myeloid, AcuteMolecular Sequence DataPolymerase Chain ReactionProspective StudiesProto-Oncogene Proteins p21(ras)Transcriptional ActivationConceptsAcute myeloid leukemia patientsMaryland Cancer CenterMyeloid leukemia patientsAcute myelogenous leukemiaRAS gene activationProspective cohortCancer CenterLeukemia patientsPrecise prevalenceMyelogenous leukemiaNRAS mutationsRAS activationRAS mutationsGene point mutationsBiologic parametersLarger studyHuman cancersPatientsAMLProtooncogene activationExon mutationsActivationCell DNAMutationsPoint mutations