Featured Publications
Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice
Roy S, Li Z, Guo Z, Long K, Rehrl S, Tian X, Dong K, Besse W. Dnajb11-Kidney Disease Develops from Reduced Polycystin-1 Dosage but not Unfolded Protein Response in Mice. Journal Of The American Society Of Nephrology 2023, 34: 1521-1534. PMID: 37332102, PMCID: PMC10482070, DOI: 10.1681/asn.0000000000000164.Peer-Reviewed Original ResearchConceptsUnfolded protein responseAutosomal dominant tubulointerstitial kidney diseaseAutosomal dominant polycystic kidney diseasePolycystin-1Autosomal-dominant polycystic kidney diseaseProtein responseTubulointerstitial kidney diseaseKidney diseaseRenal failureRenal failure in adulthoodPolycystic kidney diseaseUnfolded protein response activationFull-length proteinProteins polycystin-1C-terminal fragmentCystic kidneysSite of maturationCystic kidney dysplasiaKidney disease pathogenesisHeterozygous inactivating mutationsHsp40 cochaperonesEndoplasmic reticulumMouse model studiesConditional allelesDNAJB11ALG9 Mutation Carriers Develop Kidney and Liver Cysts
Besse W, Chang AR, Luo JZ, Triffo WJ, Moore BS, Gulati A, Hartzel DN, Mane S, Center R, Torres VE, Somlo S, Mirshahi T. ALG9 Mutation Carriers Develop Kidney and Liver Cysts. Journal Of The American Society Of Nephrology 2019, 30: 2091-2102. PMID: 31395617, PMCID: PMC6830805, DOI: 10.1681/asn.2019030298.Peer-Reviewed Original ResearchConceptsProteins polycystin-1Autosomal dominant polycystic kidney diseaseDisease genesRare loss-of-function variantsN-glycan precursorsNovel disease genesLoss-of-function variantsEndoplasmic reticulum lumenLoss-of-function mutationsMonogenic kidney diseaseWhole-exome sequencingGenotype-phenotype correlationProtein biogenesisProtein maturationReticulum lumenPolycystin-1Endoplasmic reticulumGene productsPopulation-based cohortCell-based assaysPhenotypic characterizationPolycystic phenotypeMutation carrier stateDefective glycosylationDominant polycystic kidney diseaseIsolated polycystic liver disease genes define effectors of polycystin-1 function
Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. Journal Of Clinical Investigation 2017, 127: 1772-1785. PMID: 28375157, PMCID: PMC5409105, DOI: 10.1172/jci90129.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCalcium-Binding ProteinsCell Line, TransformedCystsEndoplasmic ReticulumFemaleGenome-Wide Association StudyGlucosidasesGlucosyltransferasesHeterozygoteHumansIntracellular Signaling Peptides and ProteinsLiver DiseasesMaleMembrane ProteinsMiceMolecular ChaperonesMutationRNA-Binding ProteinsSEC Translocation ChannelsTRPP Cation ChannelsConceptsPolycystin-1 functionPolycystin-1Protein biogenesis pathwaysGenome-wide basisPolycystic liver diseaseLoss-of-function mutationsWhole-exome sequencingHeterozygous loss-of-function mutationsBiogenesis pathwayLoss of functionAdditional genesDisease genesGene productsCell line modelsCandidate genesExome sequencingEndoplasmic reticulumCausative genesFunction mutationsGenesAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseSec63Defective maturationKidney cystsAdult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease.
Besse W, Roosendaal C, Tuccillo L, Roy SG, Gallagher AR, Somlo S. Adult Inactivation of the Recessive Polycystic Kidney Disease Gene Causes Polycystic Liver Disease. Kidney360 2020, 1: 1068-1076. PMID: 33554127, PMCID: PMC7861569, DOI: 10.34067/kid.0002522020.Peer-Reviewed Original ResearchConceptsAutosomal recessive polycystic kidney diseaseSomatic second-hit mutationsAutosomal dominant polycystic kidney diseaseSecond-hit mutationsPolycystic liver diseaseLiver phenotypePolycystic kidney diseaseBile duct homeostasisSecond hit mutationLiver cystsLiver diseaseKidney diseaseCyst formationGenetic interactionsPattern of inheritanceDisease genesRecessive polycystic kidney diseaseGermline inheritanceDominant polycystic kidney diseaseDuctal plate formationWeeks of ageRecessive genotypeSubset of adultsSomatic mutationsPlate formatMonoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease
Gall E, Olson RJ, Besse W, Heyer CM, Gainullin VG, Smith JM, Audrézet MP, Hopp K, Porath B, Shi B, Baheti S, Senum SR, Arroyo J, Madsen CD, Férec C, Joly D, Jouret F, Fikri-Benbrahim O, Charasse C, Coulibaly JM, Yu AS, Khalili K, Pei Y, Somlo S, Le Meur Y, Torres VE, Group G, Group T, Disease T, Harris PC. Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease. American Journal Of Human Genetics 2018, 102: 832-844. PMID: 29706351, PMCID: PMC5986722, DOI: 10.1016/j.ajhg.2018.03.013.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingEnd-stage renal diseaseAutosomal dominant polycystic kidney diseasePhenotypically similar familiesNext-generation sequencingDevelopment of kidney cystsCystic kidneysPolycystic kidney diseaseTargeted next-generation sequencingFrameshift changesInterstitial fibrosisKidney diseasePhenotypic hybridsMissense variantsMembrane proteinsTrafficking defectsADTKDEpisodes of goutLate-onset end-stage renal diseaseProgressive interstitial fibrosisAffected membersMultigenerational familiesCo-factorPhenotypic overlapPartial phenotypic overlapA noncoding variant in GANAB explains isolated polycystic liver disease (PCLD) in a large family
Besse W, Choi J, Ahram D, Mane S, Sanna‐Cherchi S, Torres V, Somlo S. A noncoding variant in GANAB explains isolated polycystic liver disease (PCLD) in a large family. Human Mutation 2018, 39: 378-382. PMID: 29243290, PMCID: PMC5805583, DOI: 10.1002/humu.23383.Peer-Reviewed Original ResearchConceptsLoss-of-function variantsSequence analysis pipelineWhole-exome sequencing analysisExome sequencing dataExome sequencing analysisBase pair deletionSkipping of exonIsolated polycystic liver diseaseNoncoding variantsLinkage analysisDisease genesSequence dataGene discoveryMinigene assayLinkage disequilibriumCoding regionSNP genotypingSequence analysisGenomic evaluationPolycystic liver diseaseSplice donorIdentified mutationsMutation detectionPair deletionGANABGenetic Analysis of Severe Polycystic Liver Disease in Japan
Mizuno H, Besse W, Sekine A, Long K, Kurihara S, Oba Y, Yamanouchi M, Hasegawa E, Suwabe T, Sawa N, Ubara Y, Somlo S, Hoshino J. Genetic Analysis of Severe Polycystic Liver Disease in Japan. Kidney360 2024, 5: 1106-1115. PMID: 38689396, PMCID: PMC11371350, DOI: 10.34067/kid.0000000000000461.Peer-Reviewed Original ResearchSevere polycystic liver diseaseAutosomal dominant polycystic kidney diseaseDisease genesPolycystic liver diseasePKD2 patientsGenetic analysisWhole-exome sequencingSuspected pathogenic variantsLiver diseaseSpectrum of phenotypesPKD2 variantsExome sequencingAutosomal dominant polycystic kidney disease cohortPathogenic variantsPKD2PKD1Genetic etiologyDominant polycystic kidney diseaseGenesPolycystic kidney diseaseKidney cystsNo significant differenceKidney volumePLD patientsKidney diseaseAdvancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group
Franceschini N, Feldman D, Berg J, Besse W, Chang A, Dahl N, Gbadegesin R, Pollak M, Rasouly H, Smith R, Winkler C, Gharavi A, Group N, Ars E, Bekheirnia M, Bier L, Bleyer A, Fuller L, Halbritter J, Harris P, Kiryluk K, Knoers N, Kopp J, Kramer H, Lagas S, Lieske J, Lu W, Mannon R, Markowitz G, Moe O, Nadkarni G, Nast C, Parekh R, Pei Y, Reed K, Rehm H, Richards D, Roberts M, Sabatello M, Salant D, Sampson M, Sanna-Cherchi S, Santoriello D, Sedor J, Sneddon T, Watnick T, Wilfond B, Williams W, Wong C. Advancing Genetic Testing in Kidney Diseases: Report From a National Kidney Foundation Working Group. American Journal Of Kidney Diseases 2024 PMID: 39033956, DOI: 10.1053/j.ajkd.2024.05.010.Peer-Reviewed Original ResearchGenetic testingAllied health professionalsImplementation of genetic testingModified Delphi processChronic kidney diseaseScreening of kidney diseasesHealth professionalsWorking GroupKidney diseaseGenetic risk factorsDelphi processWorking group of expertsNational Kidney FoundationPolygenic causeDisease of multiple causesClinical decisionsRisk factorsGroup of expertsCause of kidney diseaseKidney FoundationGenetic basisMultiple causesGroup consensusGenetic causeMonogenic disorders
2023
Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease
Schönauer R, Sierks D, Boerrigter M, Jawaid T, Caroff L, Audrezet M, Friedrich A, Shaw M, Degenhardt J, Forberger M, de Fallois J, Bläker H, Bergmann C, Gödiker J, Schindler P, Schlevogt B, Müller R, Berg T, Patterson I, Griffiths W, Sayer J, Consortium G, Ambrose J, Arumugam P, Bevers R, Bleda M, Boardman-Pretty F, Boustred C, Brittain H, Caulfield M, Chan G, Elgar G, Fowler T, Giess A, Hamblin A, Henderson S, Hubbard T, Jackson R, Jones L, Kasperaviciute D, Kayikci M, Kousathanas A, Lahnstein L, Leigh S, Leong I, Lopez J, Maleady-Crowe F, McEntagart M, Minneci F, Moutsianas L, Mueller M, Murugaesu N, Need A, O’Donovan P, Odhams C, Patch C, Pereira M, Perez-Gil D, Pullinger J, Rahim T, Rendon A, Rogers T, Savage K, Sawant K, Scott R, Siddiq A, Sieghart A, Smith S, Sosinsky A, Stuckey A, Tanguy M, Tavares A, Thomas E, Thompson S, Tucci A, Welland M, Williams E, Witkowska K, Wood S, Popp B, Torres V, Hogan M, Somlo S, Watnick T, Nevens F, Besse W, Gall E, Harris P, Drenth J, Halbritter J. Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease. Gastroenterology 2023, 166: 902-914. PMID: 38101549, DOI: 10.1053/j.gastro.2023.12.007.Peer-Reviewed Original ResearchAutosomal dominant polycystic liver diseasePolycystic liver diseaseDisease-related hospitalizationsLiver diseaseLiver eventsPathogenic variantsPrimary clinical end pointCombination of female sexCohort of patientsClinical end pointsInternational multicenter cohortPrediction of disease progressionGenotype-phenotype correlationPrimary clinical endpointTotal liver volumeUnderlying genetic defectSymptomatic hepatomegalyDesign of randomized controlled trialsRandomized controlled trialsFemale patientsIndependent of sexMulticenter cohortFemale preponderanceRare conditionSymptomatic diseaseCombined Consideration of Sex, Genotype, and Total Liver Volume Progression Determines the Risk of Hospitalization in an International Multicenter Cohort of Autosomal Dominant Polycystic Liver Disease
Sierks D, Schönauer R, Boerrigter M, Jawaid T, Audrezet M, Caroff L, Degenhardt J, de Fallois J, Schlevogt B, Berg T, Nevens F, Watnick T, Sayer J, Besse W, Gall E, Harris P, Drenth J, Halbritter J. Combined Consideration of Sex, Genotype, and Total Liver Volume Progression Determines the Risk of Hospitalization in an International Multicenter Cohort of Autosomal Dominant Polycystic Liver Disease. Journal Of The American Society Of Nephrology 2023, 34: 934-935. DOI: 10.1681/asn.20233411s1934c.Peer-Reviewed Original ResearchCystic Kidney Diseases in Children and Adults: Differences and Gaps in Clinical Management
Hanna C, Iliuta I, Besse W, Mekahli D, Chebib F. Cystic Kidney Diseases in Children and Adults: Differences and Gaps in Clinical Management. Seminars In Nephrology 2023, 43: 151434. PMID: 37996359, DOI: 10.1016/j.semnephrol.2023.151434.Peer-Reviewed Original ResearchConceptsCystic kidney diseaseKidney diseaseAutosomal dominant polycystic kidney diseaseAutosomal-dominant polycystic kidney diseasePolycystic kidney diseaseClinical managementDifferential diagnosisProgressive autosomal dominant polycystic kidney diseaseWide differential diagnosisKidney cystsV2 receptor antagonistKidney cystic diseaseDiagnosis of inherited disordersNext-generation sequencingRadiologic characteristicsKidney functionExtrarenal manifestationsFuture pregnanciesUnderlying conditionCystic diseaseLikely diagnosisFamily historyExtrarenal featuresPediatric diagnosesRecurrence riskKidneyNetwork: using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease
Boulogne F, Claus L, Wiersma H, Oelen R, Schukking F, de Klein N, Li S, Westra H, van der Zwaag B, van Reekum F, Sierks D, Schönauer R, Li Z, Bijlsma E, Bos W, Halbritter J, Knoers N, Besse W, Deelen P, Franke L, van Eerde A. KidneyNetwork: using kidney-derived gene expression data to predict and prioritize novel genes involved in kidney disease. European Journal Of Human Genetics 2023, 31: 1300-1308. PMID: 36807342, PMCID: PMC10620423, DOI: 10.1038/s41431-023-01296-x.Peer-Reviewed Original ResearchConceptsCo-expression networkTissue-specific expressionCandidate genesGene functionPhenotypic consequences of genetic variationPathogenic variantsConsequences of genetic variationInterpretation of genetic variantsGenetic causeRare variantsGene-phenotype associationsHereditary kidney diseaseExome sequencing dataDisease-associated genesGene expression dataPlausible candidate genesCandidate gene prioritizationKidney disease phenotypesUnbiased mannerCystic kidneysNovel genesGenetic variationPhenotypic consequencesGene prioritizationSequence data
2022
A pathogenic variant of TULP3 causes renal and hepatic fibrocystic disease
Khamirani H, Palicharla VR, Dastgheib SA, Dianatpour M, Imanieh MH, Tabei SS, Besse W, Mukhopadhyay S, Liem KF. A pathogenic variant of TULP3 causes renal and hepatic fibrocystic disease. Frontiers In Genetics 2022, 13: 1021037. PMID: 36276950, PMCID: PMC9585244, DOI: 10.3389/fgene.2022.1021037.Peer-Reviewed Original ResearchTubby-like protein 3Tubby domainPatient variantsC-terminal tubby domainAssociate with phosphoinositidesRecessive deleterious mutationsMembrane-associated proteinsInner medullary collecting duct 3 cellsDuct 3 cellsHomozygous missense mutationConserved domainsProtein traffickingIntraflagellar transportTrafficking proteinsDeleterious mutationsPatient mutationsCritical residuesMissense mutationsTULP3Pathogenic variantsLike protein 3Phenotypic spectrumMutationsCiliary dysfunctionProtein 3A Practical Guide to Genetic Testing for Kidney Disorders of Unknown Etiology
Aron AW, Dahl NK, Besse W. A Practical Guide to Genetic Testing for Kidney Disorders of Unknown Etiology. Kidney360 2022, 3: 1640-1651. PMID: 36245662, PMCID: PMC9528385, DOI: 10.34067/kid.0007552021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsClinical genetic testingGenetic testingIdentification of pathogenic variantsLimitations of genetic testingKidney-related disordersOut-of-pocket costsRisks of testingVariant nomenclatureProvider educationPathogenic variantsGene panelPatient's desireDiagnosis of kidney diseaseProvidersFollow-up investigationKidney diseaseDiagnostic utilityDiagnostic limitationsKidney disordersValuable diagnostic toolUnknown etiologyGenetic risk allelesUndetermined causeGuide managementDiagnosisAn update on ductal plate malformations and fibropolycystic diseases of the liver
Mirza H, Besse W, Somlo S, Weinreb J, Kenney B, Jain D. An update on ductal plate malformations and fibropolycystic diseases of the liver. Human Pathology 2022, 132: 102-113. PMID: 35777701, DOI: 10.1016/j.humpath.2022.06.022.Peer-Reviewed Original ResearchConceptsDuctal plate malformationLiver diseaseAdult polycystic liver diseaseAutosomal dominant polycystic kidneyFibropolycystic liver diseaseIsolated liver involvementCongenital hepatic fibrosisPolycystic liver diseaseVon Meyenburg complexesGenetic underpinningsMultiple clinical phenotypesFibropolycystic diseasePortal hypertensionCaroli's diseaseLiver involvementLiver cystsMeyenburg complexesHepatic fibrosisFibrocystic lesionsHepatocellular malignanciesCyst enlargementAbnormal organ developmentPolycystic kidneysAnimal modelsHepatocellular malignancyGenetic Diseases Associated with Tubulointerstitial Nephritis
Wolf M, Besse W, Bleyer A, Dahl N. Genetic Diseases Associated with Tubulointerstitial Nephritis. 2022, 139-160. DOI: 10.1007/978-3-030-93438-5_11.ChaptersAutosomal dominant tubulointerstitial kidney diseaseTubulointerstitial kidney diseaseKidney diseaseExtrarenal manifestationsProgressive chronic kidney diseaseBland urinary sedimentChronic kidney diseaseNormal-sized kidneysMedullary cystic diseaseImmunosuppressive therapyKidney transplantationTubulointerstitial nephritisChronic inflammationCystic diseaseFamily historyUrinary sedimentEarly diagnosisHyperuricemic nephropathyClinical descriptionDiseaseSize kidneysGenetic formsDiagnosisInappropriate useOverlapping features
2020
Genetic Analysis in Kidney Disease: Advancing Clinical Diagnosis and Research Discovery.
Besse W. Genetic Analysis in Kidney Disease: Advancing Clinical Diagnosis and Research Discovery. Kidney360 2020, 1: 720-723. PMID: 34327334, PMCID: PMC8317592, DOI: 10.34067/kid.0003632020.Commentaries, Editorials and LettersLarge Deletions in GANAB and SEC63 Explain 2 Cases of Polycystic Kidney and Liver Disease
Wilson EM, Choi J, Torres VE, Somlo S, Besse W. Large Deletions in GANAB and SEC63 Explain 2 Cases of Polycystic Kidney and Liver Disease. Kidney International Reports 2020, 5: 727-731. PMID: 32405593, PMCID: PMC7210741, DOI: 10.1016/j.ekir.2020.01.009.Peer-Reviewed Original Research
2019
Collagen IV Gene Mutations in Adults With Bilateral Renal Cysts and CKD
Gulati A, Sevillano AM, Praga M, Gutierrez E, Alba I, Dahl NK, Besse W, Choi J, Somlo S. Collagen IV Gene Mutations in Adults With Bilateral Renal Cysts and CKD. Kidney International Reports 2019, 5: 103-108. PMID: 31922066, PMCID: PMC6943786, DOI: 10.1016/j.ekir.2019.09.004.Peer-Reviewed Original Research
2016
Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation
Besse W, Mansour S, Jatwani K, Nast CC, Brewster UC. Collapsing glomerulopathy in a young woman with APOL1 risk alleles following acute parvovirus B19 infection: a case report investigation. BMC Nephrology 2016, 17: 125. PMID: 27600725, PMCID: PMC5013576, DOI: 10.1186/s12882-016-0330-7.Peer-Reviewed Case Reports and Technical NotesConceptsParvovirus B19 infectionAcute parvovirus B19 infectionFocal segmental glomerulosclerosisHuman immunodeficiency virusAPOL1 risk allelesB19 infectionRisk allelesCollapsing variant of focal segmental glomerulosclerosisVariant of focal segmental glomerulosclerosisPublished case reportsHuman immunodeficiency virus (HIV) infectionCaribbean-American womenInfection of podocytesAcute parvovirus infectionImmunodeficiency virus infectionRapid clinical courseFetal demiseForms of FSGSLight microscopy findingsClinical courseHIV-negativeImmunodeficiency virusRenal biopsyKidney biopsyParvovirus B19