000137691 001__ 137691
000137691 005__ 20240321220309.0
000137691 0247_ $$2doi$$a10.1016/j.ajhg.2014.10.013
000137691 0247_ $$2pmid$$apmid:25466870
000137691 0247_ $$2pmc$$apmc:PMC4259973
000137691 0247_ $$2ISSN$$a0002-9297
000137691 0247_ $$2ISSN$$a1537-6605
000137691 0247_ $$2altmetric$$aaltmetric:2909138
000137691 037__ $$aDZNE-2020-04013
000137691 041__ $$aEnglish
000137691 082__ $$a570
000137691 1001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b0$$eFirst author
000137691 245__ $$aAbsence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration.
000137691 260__ $$aNew York, NY$$bElsevier$$c2014
000137691 264_1 $$2Crossref$$3print$$bElsevier BV$$c2014-12-01
000137691 3367_ $$2DRIVER$$aarticle
000137691 3367_ $$2DataCite$$aOutput Types/Journal article
000137691 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1710759727_18975
000137691 3367_ $$2BibTeX$$aARTICLE
000137691 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000137691 3367_ $$00$$2EndNote$$aJournal Article
000137691 520__ $$aDiabetes mellitus and neurodegeneration are common diseases for which shared genetic factors are still only partly known. Here, we show that loss of the BiP (immunoglobulin heavy-chain binding protein) co-chaperone DNAJC3 leads to diabetes mellitus and widespread neurodegeneration. We investigated three siblings with juvenile-onset diabetes and central and peripheral neurodegeneration, including ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. Exome sequencing identified a homozygous stop mutation in DNAJC3. Screening of a diabetes database with 226,194 individuals yielded eight phenotypically similar individuals and one family carrying a homozygous DNAJC3 deletion. DNAJC3 was absent in fibroblasts from all affected subjects in both families. To delineate the phenotypic and mutational spectrum and the genetic variability of DNAJC3, we analyzed 8,603 exomes, including 506 from families affected by diabetes, ataxia, upper-motor-neuron damage, peripheral neuropathy, or hearing loss. This analysis revealed only one further loss-of-function allele in DNAJC3 and no further associations in subjects with only a subset of the features of the main phenotype. Our findings demonstrate that loss-of-function DNAJC3 mutations lead to a monogenic, recessive form of diabetes mellitus in humans. Moreover, they present a common denominator for diabetes and widespread neurodegeneration. This complements findings from mice in which knockout of Dnajc3 leads to diabetes and modifies disease in a neurodegenerative model of Marinesco-Sjögren syndrome.
000137691 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000137691 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x1
000137691 542__ $$2Crossref$$i2014-12-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/
000137691 542__ $$2Crossref$$i2015-06-04$$uhttps://www.elsevier.com/open-access/userlicense/1.0/
000137691 588__ $$aDataset connected to CrossRef, PubMed,
000137691 650_7 $$2NLM Chemicals$$aDNAJC3 protein, human
000137691 650_7 $$2NLM Chemicals$$aHSP40 Heat-Shock Proteins
000137691 650_7 $$2NLM Chemicals$$aHeat-Shock Proteins
000137691 650_7 $$0YCYIS6GADR$$2NLM Chemicals$$amolecular chaperone GRP78
000137691 650_2 $$2MeSH$$aEndoplasmic Reticulum Chaperone BiP
000137691 650_2 $$2MeSH$$aAdolescent
000137691 650_2 $$2MeSH$$aAdult
000137691 650_2 $$2MeSH$$aAtaxia: genetics
000137691 650_2 $$2MeSH$$aDiabetes Mellitus, Type 1: diagnostic imaging
000137691 650_2 $$2MeSH$$aDiabetes Mellitus, Type 1: genetics
000137691 650_2 $$2MeSH$$aExome: genetics
000137691 650_2 $$2MeSH$$aFemale
000137691 650_2 $$2MeSH$$aFibroblasts
000137691 650_2 $$2MeSH$$aGene Expression Regulation
000137691 650_2 $$2MeSH$$aHSP40 Heat-Shock Proteins: genetics
000137691 650_2 $$2MeSH$$aHSP40 Heat-Shock Proteins: metabolism
000137691 650_2 $$2MeSH$$aHeat-Shock Proteins: genetics
000137691 650_2 $$2MeSH$$aHomozygote
000137691 650_2 $$2MeSH$$aHumans
000137691 650_2 $$2MeSH$$aMale
000137691 650_2 $$2MeSH$$aModels, Molecular
000137691 650_2 $$2MeSH$$aMultiple System Atrophy: diagnostic imaging
000137691 650_2 $$2MeSH$$aMultiple System Atrophy: genetics
000137691 650_2 $$2MeSH$$aMutation
000137691 650_2 $$2MeSH$$aPedigree
000137691 650_2 $$2MeSH$$aPhenotype
000137691 650_2 $$2MeSH$$aRadiography
000137691 650_2 $$2MeSH$$aSequence Analysis, DNA
000137691 650_2 $$2MeSH$$aYoung Adult
000137691 7001_ $$aHaack, Tobias B$$b1
000137691 7001_ $$aKopajtich, Robert$$b2
000137691 7001_ $$aGorza, Matteo$$b3
000137691 7001_ $$aRapaport, Doron$$b4
000137691 7001_ $$aGreiner, Markus$$b5
000137691 7001_ $$0P:(DE-2719)9000290$$aSchoenfeld, Caroline$$b6
000137691 7001_ $$aFreiberg, Clemens$$b7
000137691 7001_ $$aSchorr, Stefan$$b8
000137691 7001_ $$aHoll, Reinhard W$$b9
000137691 7001_ $$aGonzalez, Michael A$$b10
000137691 7001_ $$aFritsche, Andreas$$b11
000137691 7001_ $$aFallier-Becker, Petra$$b12
000137691 7001_ $$aZimmermann, Richard$$b13
000137691 7001_ $$aStrom, Tim M$$b14
000137691 7001_ $$0P:(DE-HGF)0$$aMeitinger, Thomas$$b15
000137691 7001_ $$aZüchner, Stephan$$b16
000137691 7001_ $$0P:(DE-2719)2812018$$aSchüle, Rebecca$$b17
000137691 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b18
000137691 7001_ $$aProkisch, Holger$$b19
000137691 77318 $$2Crossref$$3journal-article$$a10.1016/j.ajhg.2014.10.013$$b : Elsevier BV, 2014-12-01$$n6$$p689-697$$tThe American Journal of Human Genetics$$v95$$x0002-9297$$y2014
000137691 773__ $$0PERI:(DE-600)1473813-2$$a10.1016/j.ajhg.2014.10.013$$gVol. 95, no. 6, p. 689 - 697$$n6$$p689-697$$q95:6<689 - 697$$tThe American journal of human genetics$$v95$$x0002-9297$$y2014
000137691 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4259973
000137691 8564_ $$uhttps://pub.dzne.de/record/137691/files/DZNE-2020-04013_Restricted.pdf
000137691 8564_ $$uhttps://pub.dzne.de/record/137691/files/DZNE-2020-04013_Restricted.pdf?subformat=pdfa$$xpdfa
000137691 909CO $$ooai:pub.dzne.de:137691$$pVDB
000137691 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811275$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000137691 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000290$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b6$$kDZNE
000137691 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812018$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b17$$kDZNE
000137691 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810795$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b18$$kDZNE
000137691 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000137691 9131_ $$0G:(DE-HGF)POF3-345$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vPopulation Studies and Genetics$$x1
000137691 9141_ $$y2014
000137691 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000137691 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000137691 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000137691 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central
000137691 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bAM J HUM GENET : 2017
000137691 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000137691 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000137691 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000137691 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000137691 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000137691 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000137691 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine
000137691 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000137691 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000137691 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bAM J HUM GENET : 2017
000137691 9201_ $$0I:(DE-2719)1210000$$kAG Gasser$$lParkinson Genetics$$x0
000137691 9201_ $$0I:(DE-2719)6000018$$kTübingen common$$lTübingen common$$x1
000137691 9201_ $$0I:(DE-2719)5000024$$kAG Maetzler$$lFunctional Neurogeriatrics$$x2
000137691 9201_ $$0I:(DE-2719)5000005$$kAG Schöls$$lClinical Neurogenetics$$x3
000137691 980__ $$ajournal
000137691 980__ $$aVDB
000137691 980__ $$aI:(DE-2719)1210000
000137691 980__ $$aI:(DE-2719)6000018
000137691 980__ $$aI:(DE-2719)5000024
000137691 980__ $$aI:(DE-2719)5000005
000137691 980__ $$aUNRESTRICTED