2023
Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations
Zhao S, Mekbib K, van der Ent M, Allington G, Prendergast A, Chau J, Smith H, Shohfi J, Ocken J, Duran D, Furey C, Hao L, Duy P, Reeves B, Zhang J, Nelson-Williams C, Chen D, Li B, Nottoli T, Bai S, Rolle M, Zeng X, Dong W, Fu P, Wang Y, Mane S, Piwowarczyk P, Fehnel K, See A, Iskandar B, Aagaard-Kienitz B, Moyer Q, Dennis E, Kiziltug E, Kundishora A, DeSpenza T, Greenberg A, Kidanemariam S, Hale A, Johnston J, Jackson E, Storm P, Lang S, Butler W, Carter B, Chapman P, Stapleton C, Patel A, Rodesch G, Smajda S, Berenstein A, Barak T, Erson-Omay E, Zhao H, Moreno-De-Luca A, Proctor M, Smith E, Orbach D, Alper S, Nicoli S, Boggon T, Lifton R, Gunel M, King P, Jin S, Kahle K. Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations. Nature Communications 2023, 14: 7452. PMID: 37978175, PMCID: PMC10656524, DOI: 10.1038/s41467-023-43062-z.Peer-Reviewed Original ResearchConceptsEphrin receptor B4Galen malformationBrain arteriovenous malformationsP120 RasGAPTransmitted variantsArteriovenous malformationsDe novo variantsSingle-cell transcriptomesSignificant burdenCerebrovascular developmentIntegrative genomic analysisEndothelial cellsVenous networkAdditional probandsMalformationsNovo variantsMissense variantsGenomic analysisDevelopmental angiogenesisVascular developmentDamaging variantsVeinRasGAPIntegrated analysisPatients
2022
OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis
Majmundar A, Widmeier E, Heneghan J, Daga A, Wu C, Buerger F, Hugo H, Ullah I, Amar A, Ottlewski I, Braun D, Jobst-Schwan T, Lawson J, Zahoor M, Rodig N, Tasic V, Nelson C, Khaliq S, Schönauer R, Halbritter J, Sayer J, Fathy H, Baum M, Shril S, Mane S, Alper S, Hildebrandt F. OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis. Genetics In Medicine 2022, 25: 100351. PMID: 36571463, PMCID: PMC9992313, DOI: 10.1016/j.gim.2022.11.019.Peer-Reviewed Original ResearchConceptsExome sequencingChronic kidney diseaseStrong amino acid conservationSignificant patient morbidityCalcium oxalate nephrolithiasisMissense variantsAutosomal dominant inheritance patternTransepithelial calcium transportAmino acid conservationCandidate disease genesDominant inheritance patternCausative genetic variantsKidney diseasePatient morbidityExome Aggregation ConsortiumNC cohortRisk factorsOxalate nephrolithiasisDistal nephronNephrocalcinosisNephrolithiasisLoss of functionChloride-bicarbonate exchangerReceptor 1Genomic approaches
2018
A 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