{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361137044772459520.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1016/j.ajhg.2018.03.013"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0002929718301022?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0002929718301022?httpAccept=text/plain"}},{"identifier":{"@type":"PMID","@value":"29777155"}}],"dc:title":[{"@value":"Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease"}],"description":[{"notation":[{"@value":"Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381137044772459650","@type":"Researcher","foaf:name":[{"@value":"Emilie Cornec-Le Gall"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459662","@type":"Researcher","foaf:name":[{"@value":"Rory J. Olson"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459649","@type":"Researcher","foaf:name":[{"@value":"Whitney Besse"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459522","@type":"Researcher","foaf:name":[{"@value":"Christina M. Heyer"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459526","@type":"Researcher","foaf:name":[{"@value":"Vladimir G. Gainullin"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459525","@type":"Researcher","foaf:name":[{"@value":"Jessica M. Smith"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459659","@type":"Researcher","foaf:name":[{"@value":"Marie-Pierre Audrézet"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459664","@type":"Researcher","foaf:name":[{"@value":"Katharina Hopp"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459524","@type":"Researcher","foaf:name":[{"@value":"Binu Porath"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459660","@type":"Researcher","foaf:name":[{"@value":"Beili Shi"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459521","@type":"Researcher","foaf:name":[{"@value":"Saurabh Baheti"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459657","@type":"Researcher","foaf:name":[{"@value":"Sarah R. Senum"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459667","@type":"Researcher","foaf:name":[{"@value":"Jennifer Arroyo"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459648","@type":"Researcher","foaf:name":[{"@value":"Charles D. Madsen"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459658","@type":"Researcher","foaf:name":[{"@value":"Claude Férec"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459661","@type":"Researcher","foaf:name":[{"@value":"Dominique Joly"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459654","@type":"Researcher","foaf:name":[{"@value":"François Jouret"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459655","@type":"Researcher","foaf:name":[{"@value":"Oussamah Fikri-Benbrahim"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459651","@type":"Researcher","foaf:name":[{"@value":"Christophe Charasse"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459656","@type":"Researcher","foaf:name":[{"@value":"Jean-Marie Coulibaly"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459652","@type":"Researcher","foaf:name":[{"@value":"Alan S. Yu"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459653","@type":"Researcher","foaf:name":[{"@value":"Korosh Khalili"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459666","@type":"Researcher","foaf:name":[{"@value":"York Pei"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459665","@type":"Researcher","foaf:name":[{"@value":"Stefan Somlo"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459520","@type":"Researcher","foaf:name":[{"@value":"Yannick Le Meur"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459663","@type":"Researcher","foaf:name":[{"@value":"Vicente E. Torres"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137044772459523","@type":"Researcher","foaf:name":[{"@value":"Peter C. Harris"}]}],"contributor":[{"@id":"https://cir.nii.ac.jp/crid/1893679867524912399","@type":"Researcher","foaf:name":[{"@value":"Division of Nephrology and Hypertension ; Mayo Clinic"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912405","@type":"Researcher","foaf:name":[{"@value":"Department of Biochemistry and Molecular Biology ; Mayo Clinic"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912422","@type":"Researcher","foaf:name":[{"@value":"Service de Nephrologie ; Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912416","@type":"Researcher","foaf:name":[{"@value":"Yale School of Medicine [New Haven, Connecticut] (YSM)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912408","@type":"Researcher","foaf:name":[{"@value":"Department of Computer Science and Software Engineering (CCSE) ; University of Melbourne"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912411","@type":"Researcher","foaf:name":[{"@value":"Yale University School of Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912517","@type":"Researcher","foaf:name":[{"@value":"Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB) ; Institut Brestois Santé Agro Matière (IBSAM) ; Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912415","@type":"Researcher","foaf:name":[{"@value":"CH de Saint-Brieuc ; CH de Saint-Brieuc"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912389","@type":"Researcher","foaf:name":[{"@value":"Divisions of Nephrology and Genomic Medicine ; University of Toronto-University Health Network"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912401","@type":"Researcher","foaf:name":[{"@value":"Department of Internal Medicine ; Yale University School of Medicine"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912388","@type":"Researcher","foaf:name":[{"@value":"Lymphocyte B et Auto-immunité (LBAI) ; Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM) ; Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912396","@type":"Researcher","foaf:name":[{"@value":"CHU de Saint-Brieuc"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912390","@type":"Researcher","foaf:name":[{"@value":"Mayo Clinic [Rochester]"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912386","@type":"Researcher","foaf:name":[{"@value":"Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB) ; EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM) ; Université de Brest (UBO)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912417","@type":"Researcher","foaf:name":[{"@value":"Division of Nephrology, Toronto (University Health Network)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912384","@type":"Researcher","foaf:name":[{"@value":"Génétique moléculaire et génétique épidémiologique ; Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912413","@type":"Researcher","foaf:name":[{"@value":"Évolution, génomes, comportement et écologie (EGCE) ; Université Paris-Sud - Paris 11 (UP11)-IRD-Centre National de la Recherche Scientifique (CNRS)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912524","@type":"Researcher","foaf:name":[{"@value":"Division of Nephrology, Liège"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912392","@type":"Researcher","foaf:name":[{"@value":"Service of Nephrology and Hemodialysis, Saintes"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912402","@type":"Researcher","foaf:name":[{"@value":"Centre hospitalier de Saint-Brieuc [Hôpital Yves Le Foll] (CH Saint-Brieuc) ; Groupement Hospitalier Territoire d'Armor (GHT Armor)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912419","@type":"Researcher","foaf:name":[{"@value":"Service de Néphrologie, CH St Brieuc"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912423","@type":"Researcher","foaf:name":[{"@value":"Institute of Geology and Geophysics [Beijing] (IGG) ; Chinese Academy of Sciences [Beijing] (CAS)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912407","@type":"Researcher","foaf:name":[{"@value":"Department of Medical Imaging [University of Toronto] ; University of Toronto"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912412","@type":"Researcher","foaf:name":[{"@value":"Divisions of Nephrology and Genomic Medicine ; University of Toronto-University Health Network [Toronto, ON, Canada]"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912522","@type":"Researcher","foaf:name":[{"@value":"Department of Internal Medicine ; Yale School of Medicine [New Haven, Connecticut] (YSM)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912420","@type":"Researcher","foaf:name":[{"@value":"Lymphocytes B, Autoimmunité et Immunothérapies (LBAI) ; Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest ; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM) ; Université de Brest (UBO)"}]},{"@id":"https://cir.nii.ac.jp/crid/1893679867524912421","@type":"Researcher","foaf:name":[{"@value":"Universidade de Aveiro"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00029297"}],"prism:publicationName":[{"@value":"The American Journal of Human Genetics"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2018-05","prism:volume":"102","prism:number":"5","prism:startingPage":"832","prism:endingPage":"844"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","https://www.elsevier.com/legal/tdmrep-license","http://www.elsevier.com/open-access/userlicense/1.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0002929718301022?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0002929718301022?httpAccept=text/plain"}],"createdAt":"2018-04-26","modifiedAt":"2025-11-02","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Adult","dc:title":"Adult"},{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=TRPP%20Cation%20Channels","dc:title":"TRPP Cation Channels"},{"@id":"https://cir.nii.ac.jp/all?q=%5BSDV%5DLife%20Sciences%20%5Bq-bio%5D","dc:title":"[SDV]Life Sciences [q-bio]"},{"@id":"https://cir.nii.ac.jp/all?q=Young%20Adult","dc:title":"Young Adult"},{"@id":"https://cir.nii.ac.jp/all?q=renal%20cystic%20disease","dc:title":"renal cystic disease"},{"@id":"https://cir.nii.ac.jp/all?q=Uromodulin","dc:title":"Uromodulin"},{"@id":"https://cir.nii.ac.jp/all?q=Exome%20Sequencing","dc:title":"Exome Sequencing"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Family","dc:title":"Family"},{"@id":"https://cir.nii.ac.jp/all?q=Amino%20Acid%20Sequence","dc:title":"Amino Acid Sequence"},{"@id":"https://cir.nii.ac.jp/all?q=pathogenic%20variants","dc:title":"pathogenic variants"},{"@id":"https://cir.nii.ac.jp/all?q=Alleles","dc:title":"Alleles"},{"@id":"https://cir.nii.ac.jp/all?q=ADPKD","dc:title":"ADPKD"},{"@id":"https://cir.nii.ac.jp/all?q=Aged","dc:title":"Aged"},{"@id":"https://cir.nii.ac.jp/all?q=Aged,%2080%20and%20over","dc:title":"Aged, 80 and over"},{"@id":"https://cir.nii.ac.jp/all?q=ADTKD","dc:title":"ADTKD"},{"@id":"https://cir.nii.ac.jp/all?q=Base%20Sequence","dc:title":"Base Sequence"},{"@id":"https://cir.nii.ac.jp/all?q=Epithelial%20Cells","dc:title":"Epithelial Cells"},{"@id":"https://cir.nii.ac.jp/all?q=HSP40%20Heat-Shock%20Proteins","dc:title":"HSP40 Heat-Shock Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Middle%20Aged","dc:title":"Middle Aged"},{"@id":"https://cir.nii.ac.jp/all?q=DNAJB11","dc:title":"DNAJB11"},{"@id":"https://cir.nii.ac.jp/all?q=Polycystic%20Kidney,%20Autosomal%20Dominant","dc:title":"Polycystic Kidney, Autosomal Dominant"},{"@id":"https://cir.nii.ac.jp/all?q=Pedigree","dc:title":"Pedigree"},{"@id":"https://cir.nii.ac.jp/all?q=Mutation","dc:title":"Mutation"},{"@id":"https://cir.nii.ac.jp/all?q=Loop%20of%20Henle","dc:title":"Loop of Henle"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=ADPLD","dc:title":"ADPLD"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360017279870136832","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mutation Analysis of Autosomal-Dominant Polycystic Kidney Disease Patients"}]},{"@id":"https://cir.nii.ac.jp/crid/1360025431115970816","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Liver‐specific <scp>DICER1</scp> syndrome model mice develop cystic liver tumors with defective primary cilia"}]},{"@id":"https://cir.nii.ac.jp/crid/1360286993864930944","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"SDF2-like protein 1 (SDF2L1) regulates the endoplasmic reticulum localization and chaperone activity of 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