Afficher la notice abrégée

De novo variants in ATP2B1 lead to neurodevelopmental delay.

dc.rights.licenseopenen_US
dc.contributor.authorRAHIMI, Meer Jacob
dc.contributor.authorURBAN, Nicole
dc.contributor.authorWEGLER, Meret
dc.contributor.authorSTICHT, Heinrich
dc.contributor.authorSCHAEFER, Michael
dc.contributor.authorPOPP, Bernt
dc.contributor.authorGAUNITZ, Frank
dc.contributor.authorMORLEO, Manuela
dc.contributor.authorNIGRO, Vincenzo
dc.contributor.authorMAITZ, Silvia
dc.contributor.authorMANCINI, Grazia M S
dc.contributor.authorRUIVENKAMP, Claudia
dc.contributor.authorSUK, Eun-Kyung
dc.contributor.authorBARTOLOMAEUS, Tobias
dc.contributor.authorMERKENSCHLAGER, Andreas
dc.contributor.authorKOBOLDT, Daniel
dc.contributor.authorBARTHOLOMEW, Dennis
dc.contributor.authorSTEGMANN, Alexander P A
dc.contributor.authorSINNEMA, Margje
dc.contributor.authorDUYNISVELD, Irma
dc.contributor.authorSALVARINOVA, Ramona
dc.contributor.authorRACE, Simone
dc.contributor.authorDE VRIES, Bert B A
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorTRIMOUILLE, Aurelien
dc.contributor.authorNAUDION, Sophie
dc.contributor.authorMAROM, Daphna
dc.contributor.authorHAMIEL, Uri
dc.contributor.authorHENIG, Noa
dc.contributor.authorDEMURGER, Florence
dc.contributor.authorRAHNER, Nils
dc.contributor.authorBARTELS, Enrika
dc.contributor.authorHAMM, J Austin
dc.contributor.authorPUTNAM, Abbey M
dc.contributor.authorPERSON, Richard
dc.contributor.authorABOU JAMRA, Rami
dc.contributor.authorOPPERMANN, Henry
dc.date.accessioned2023-07-05T09:24:50Z
dc.date.available2023-07-05T09:24:50Z
dc.date.issued2022-05-05
dc.identifier.issn1537-6605en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/183303
dc.description.abstractEnCalcium (Ca) is a universal second messenger involved in synaptogenesis and cell survival; consequently, its regulation is important for neurons. ATPase plasma membrane Ca transporting 1 (ATP2B1) belongs to the family of ATP-driven calmodulin-dependent Ca pumps that participate in the regulation of intracellular free Ca. Here, we clinically describe a cohort of 12 unrelated individuals with variants in ATP2B1 and an overlapping phenotype of mild to moderate global development delay. Additional common symptoms include autism, seizures, and distal limb abnormalities. Nine probands harbor missense variants, seven of which were in specific functional domains, and three individuals have nonsense variants. 3D structural protein modeling suggested that the variants have a destabilizing effect on the protein. We performed Ca imaging after introducing all nine missense variants in transfected HEK293 cells and showed that all variants lead to a significant decrease in Ca export capacity compared with the wild-type construct, thus proving their pathogenicity. Furthermore, we observed for the same variant set an incorrect intracellular localization of ATP2B1. The genetic findings and the overlapping phenotype of the probands as well as the functional analyses imply that de novo variants in ATP2B1 lead to a monogenic form of neurodevelopmental disorder.
dc.language.isoENen_US
dc.subject.enHEK293 Cells
dc.subject.enHumans
dc.subject.enIntellectual Disability
dc.subject.enMutation
dc.subject.enMissense
dc.subject.enNervous System Malformations
dc.subject.enNeurodevelopmental Disorders
dc.subject.enPhenotype
dc.subject.enPlasma Membrane Calcium-Transporting ATPases
dc.title.enDe novo variants in ATP2B1 lead to neurodevelopmental delay.
dc.title.alternativeAm J Hum Geneten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.ajhg.2022.03.009en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed35358416en_US
bordeaux.journalAmerican Journal of Human Geneticsen_US
bordeaux.page944-952en_US
bordeaux.volume109en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04152067
hal.version1
hal.date.transferred2023-07-05T09:25:34Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=American%20Journal%20of%20Human%20Genetics&rft.date=2022-05-05&rft.volume=109&rft.issue=5&rft.spage=944-952&rft.epage=944-952&rft.eissn=1537-6605&rft.issn=1537-6605&rft.au=RAHIMI,%20Meer%20Jacob&URBAN,%20Nicole&WEGLER,%20Meret&STICHT,%20Heinrich&SCHAEFER,%20Michael&rft.genre=article


Fichier(s) constituant ce document

Thumbnail
Nom:
MRGM_The American Journal of ...
Taille:
1.971Mo
Format:
PDF
Voir/Ouvrir

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée