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 interactionRab5Whole Exome Sequencing Reveals a Monogenic Cause of Disease in ≈43% of 35 Families With Midaortic Syndrome
Warejko JK, Schueler M, Vivante A, Tan W, Daga A, Lawson JA, Braun DA, Shril S, Amann K, Somers MJG, Rodig NM, Baum MA, Daouk G, Traum AZ, Kim HB, Vakili K, Porras D, Lock J, Rivkin MJ, Chaudry G, Smoot LB, Singh MN, Smith ER, Mane SM, Lifton RP, Stein DR, Ferguson MA, Hildebrandt F. Whole Exome Sequencing Reveals a Monogenic Cause of Disease in ≈43% of 35 Families With Midaortic Syndrome. Hypertension 2018, 71: 691-699. PMID: 29483232, PMCID: PMC5843550, DOI: 10.1161/hypertensionaha.117.10296.Peer-Reviewed Original ResearchConceptsMidaortic syndromeWhole-exome sequencingExome sequencingVascular diseaseMonogenic causesExtensive vascular diseaseSevere childhood hypertensionGenotype/phenotype correlationChildhood hypertensionRare causeEtiologic diagnosisInflammatory diseasesAbdominal aortaMolecular genetic diagnosisGenetic syndromesSyndromic diseaseWhole-exome sequencing dataDiseaseSyndromePhenotype correlationGenetic diagnosisExome sequencing dataDiagnosisCauseHigh percentageA 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