Afficher la notice abrégée

Homozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia

dc.rights.licenseopenen_US
dc.contributor.authorBARISH, Scott
dc.contributor.authorLIN, Sheng-Jia
dc.contributor.authorMAROOFIAN, Reza
dc.contributor.authorGEZDIRICI, Alper
dc.contributor.authorALHEBBY, Hamoud
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorTRIMOUILLE, Aurelien
dc.contributor.authorWABERSKI, Marta Biderman
dc.contributor.authorMITANI, Tadahiro
dc.contributor.authorHUBER, Ilka
dc.contributor.authorTVETEN, Kristian
dc.contributor.authorHOLLA, Øystein L.
dc.contributor.authorBUSK, Øyvind L.
dc.contributor.authorHOULDEN, Henry
dc.contributor.authorKARIMIANI, Ehsan Ghayoor
dc.contributor.authorTOOSI, Mehran Beiraghi
dc.contributor.authorBADV, Reza Shervin
dc.contributor.authorTORBATI, Paria Najarzadeh
dc.contributor.authorEGHBAL, Fatemeh
dc.contributor.authorAKHONDIAN, Javad
dc.contributor.authorAL SAFAR, Ayat
dc.contributor.authorALSWAID, Abdulrahman
dc.contributor.authorZIFARELLI, Giovanni
dc.contributor.authorBAUER, Peter
dc.contributor.authorMARAFI, Dana
dc.contributor.authorFATIH, Jawid M.
dc.contributor.authorHUANG, Kevin
dc.contributor.authorPETREE, Cassidy
dc.contributor.authorCALAME, Daniel G.
dc.contributor.authorVON DER LIPPE, Charlotte
dc.contributor.authorALKURAYA, Fowzan S.
dc.contributor.authorWALI, Sami
dc.contributor.authorLUPSKI, James R.
dc.contributor.authorVARSHNEY, Gaurav K.
dc.contributor.authorPOSEY, Jennifer E.
dc.contributor.authorPEHLIVAN, Davut
dc.date.accessioned2025-07-15T10:03:47Z
dc.date.available2025-07-15T10:03:47Z
dc.date.issued2024-11-07
dc.identifier.issn0002-9297en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/207328
dc.description.abstractEnWD repeat domain 83 opposite strand (WDR83OS) encodes the 106-aa (amino acid) protein Asterix, which heterodimerizes with CCDC47 to form the PAT (protein associated with ER translocon) complex. This complex functions as a chaperone for large proteins containing transmembrane domains to ensure proper folding. Until recently, little was known about the role of WDR83OS or CCDC47 in human disease traits. However, biallelic variants in CCDC47 were identified in four unrelated families with trichohepatoneurodevelopmental syndrome, characterized by a neurodevelopmental disorder (NDD) with liver dysfunction. Three affected siblings in an additional family share a homozygous truncating WDR83OS variant and a phenotype of NDD, dysmorphic features, and liver dysfunction. Using family-based rare variant analyses of exome sequencing (ES) data and case matching through GeneMatcher, we describe the clinical phenotypes of 11 additional individuals in eight unrelated families (nine unrelated families, 14 individuals in total) with biallelic putative truncating variants in WDR83OS. Consistent clinical features include NDD (14/14), facial dysmorphism (13/14), intractable itching (9/14), and elevated bile acids (5/6). Whereas bile acids were significantly elevated in 5/6 of individuals tested, bilirubin was normal and liver enzymes were normal to mildly elevated in all 14 individuals. In three of six individuals for whom longitudinal data were available, we observed a progressive reduction in relative head circumference. A zebrafish model lacking Wdr83os function further supports its role in the nervous system, craniofacial development, and lipid absorption. Taken together, our data support a disease-gene association between biallelic loss-of-function of WDR83OS and a neurological disease trait with hypercholanemia. © 2024 American Society of Human Genetics
dc.language.isoENen_US
dc.subject.enASTERIX
dc.subject.enCCDC47
dc.subject.enER translocation
dc.subject.enPAT complex
dc.subject.enWDR83OS
dc.subject.enDevelopmental delay
dc.subject.enHypercholanemia
dc.subject.enIntellectual disability
dc.subject.enPruritus
dc.title.enHomozygous variants in WDR83OS lead to a neurodevelopmental disorder with hypercholanemia
dc.title.alternativeAm J Hum Geneten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.ajhg.2024.10.002en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed39471804en_US
bordeaux.journalAmerican Journal of Human Geneticsen_US
bordeaux.page2566 – 2581en_US
bordeaux.volume111en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-05162773
hal.version1
hal.date.transferred2025-07-15T10:03:52Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=American%20Journal%20of%20Human%20Genetics&rft.date=2024-11-07&rft.volume=111&rft.issue=11&rft.spage=2566%20%E2%80%93%202581&rft.epage=2566%20%E2%80%93%202581&rft.eissn=0002-9297&rft.issn=0002-9297&rft.au=BARISH,%20Scott&LIN,%20Sheng-Jia&MAROOFIAN,%20Reza&GEZDIRICI,%20Alper&ALHEBBY,%20Hamoud&rft.genre=article


Fichier(s) constituant ce document

FichiersTailleFormatVue

Il n'y a pas de fichiers associés à ce document.

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

Afficher la notice abrégée