ALG9 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 cystsMonoallelic 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 overlapGenetic 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 disease