000600663 001__ 600663
000600663 005__ 20250724132655.0
000600663 0247_ $$2doi$$a10.3390/cells12071046
000600663 0247_ $$2datacite_doi$$a10.3204/PUBDB-2023-08086
000600663 0247_ $$2altmetric$$aaltmetric:144637958
000600663 0247_ $$2pmid$$apmid:37048120
000600663 0247_ $$2WOS$$aWOS:000969745100001
000600663 0247_ $$2openalex$$aopenalex:W4361273876
000600663 037__ $$aPUBDB-2023-08086
000600663 041__ $$aEnglish
000600663 082__ $$a570
000600663 1001_ $$0P:(DE-HGF)0$$aReid, Kimberley M.$$b0
000600663 245__ $$aLoss-of-Function Variants in DRD1 in Infantile Parkinsonism-Dystonia
000600663 260__ $$aBasel$$bMDPI$$c2023
000600663 3367_ $$2DRIVER$$aarticle
000600663 3367_ $$2DataCite$$aOutput Types/Journal article
000600663 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1728909359_4051395
000600663 3367_ $$2BibTeX$$aARTICLE
000600663 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000600663 3367_ $$00$$2EndNote$$aJournal Article
000600663 520__ $$aThe human dopaminergic system is vital for a broad range of neurological processes, including the control of voluntary movement. Here we report a proband presenting with clinical features of dopamine deficiency: severe infantile parkinsonism-dystonia, characterised by frequent oculogyric crises, dysautonomia and global neurodevelopmental impairment. CSF neurotransmitter analysis was unexpectedly normal. Triome whole-genome sequencing revealed a homozygous variant (c.110C>A, (p.T37K)) in DRD1, encoding the most abundant dopamine receptor (D1) in the central nervous system, most highly expressed in the striatum. This variant was absent from gnomAD, with a CADD score of 27.5. Using an in vitro heterologous expression system, we determined that DRD1-T37K results in loss of protein function. Structure-function modelling studies predicted reduced substrate binding, which was confirmed in vitro. Exposure of mutant protein to the selective D1 agonist Chloro APB resulted in significantly reduced cyclic AMP levels. Numerous D1 agonists failed to rescue the cellular defect, reflected clinically in the patient, who had no benefit from dopaminergic therapy. Our study identifies DRD1 as a new disease-associated gene, suggesting a crucial role for the D1 receptor in motor control. 
000600663 536__ $$0G:(DE-HGF)POF4-899$$a899 - ohne Topic (POF4-899)$$cPOF4-899$$fPOF IV$$x0
000600663 536__ $$0G:(GEPRIS)458949627$$aDFG project G:(GEPRIS)458949627 - Ganzgenom- und Transkriptomsequenzierung zur Identifizierung neuer Krankheitsgene für Dystonie (458949627)$$c458949627$$x1
000600663 588__ $$aDataset connected to CrossRef, Journals: bib-pubdb1.desy.de
000600663 693__ $$0EXP:(DE-MLZ)NOSPEC-20140101$$5EXP:(DE-MLZ)NOSPEC-20140101$$eNo specific instrument$$x0
000600663 7001_ $$0P:(DE-HGF)0$$aSteel, Dora$$b1
000600663 7001_ $$0P:(DE-H253)PIP1101921$$aNair, Sanjana$$b2
000600663 7001_ $$0P:(DE-HGF)0$$aBhate, Sanjay$$b3
000600663 7001_ $$0P:(DE-HGF)0$$aBiassoni, Lorenzo$$b4
000600663 7001_ $$0P:(DE-HGF)0$$aSudhakar, Sniya$$b5
000600663 7001_ $$0P:(DE-HGF)0$$aHeys, Michelle$$b6
000600663 7001_ $$0P:(DE-HGF)0$$aBurke, Elizabeth$$b7
000600663 7001_ $$0P:(DE-HGF)0$$aKamsteeg, Erik-Jan$$b8
000600663 7001_ $$0P:(DE-HGF)0$$aHameed, Biju$$b9
000600663 7001_ $$0P:(DE-HGF)0$$aZech, Michael$$b10
000600663 7001_ $$0P:(DE-HGF)0$$aMencacci, Niccolo E.$$b11
000600663 7001_ $$0P:(DE-HGF)0$$aBarwick, Katy$$b12
000600663 7001_ $$0P:(DE-H253)PIP1094132$$aTopf, Maya$$b13
000600663 7001_ $$0P:(DE-HGF)0$$aKurian, Manju A.$$b14$$eCorresponding author
000600663 773__ $$0PERI:(DE-600)2661518-6$$a10.3390/cells12071046$$gVol. 12, no. 7, p. 1046 -$$n7$$p1046 $$tCells$$v12$$x2073-4409$$y2023
000600663 8564_ $$uhttps://bib-pubdb1.desy.de/record/600663/files/cells-12-01046-v2.pdf$$yOpenAccess
000600663 8564_ $$uhttps://bib-pubdb1.desy.de/record/600663/files/cells-12-01046-v2.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000600663 909CO $$ooai:bib-pubdb1.desy.de:600663$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000600663 9101_ $$0I:(DE-H253)_CSSB-20140311$$6P:(DE-H253)PIP1101921$$aCentre for Structural Systems Biology$$b2$$kCSSB
000600663 9101_ $$0I:(DE-H253)_CSSB-20140311$$6P:(DE-H253)PIP1094132$$aCentre for Structural Systems Biology$$b13$$kCSSB
000600663 9101_ $$0I:(DE-HGF)0$$6P:(DE-H253)PIP1094132$$aExternal Institute$$b13$$kExtern
000600663 9131_ $$0G:(DE-HGF)POF4-899$$1G:(DE-HGF)POF4-890$$2G:(DE-HGF)POF4-800$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bProgrammungebundene Forschung$$lohne Programm$$vohne Topic$$x0
000600663 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCELLS-BASEL : 2022$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-08-01T15:15:06Z
000600663 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-08-01T15:15:06Z
000600663 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-26
000600663 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000600663 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000600663 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bCELLS-BASEL : 2022$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-26
000600663 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-26
000600663 9201_ $$0I:(DE-H253)CSSB-LIV_UKE-MT-20220525$$kCSSB-LIV/UKE-MT$$lCSSB - Leibniz-Institut für Experimentelle Virologie (LIV) / UKE - Maya Topf$$x0
000600663 980__ $$ajournal
000600663 980__ $$aVDB
000600663 980__ $$aUNRESTRICTED
000600663 980__ $$aI:(DE-H253)CSSB-LIV_UKE-MT-20220525
000600663 9801_ $$aFullTexts