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Splice site variants in the canonical donor site of exon 7 lead to intron retention in patients with syndrome.

dc.rights.licenseopenen_US
dc.contributor.authorFAUQUEUX, Jade
dc.contributor.authorBOUSSION, Simon
dc.contributor.authorTHUILLIER, Caroline
dc.contributor.authorMEURISSE, Evine
hal.structure.identifierCentre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorLACOMBE, Didier
dc.contributor.authorWILLEMS, Marjolaine
dc.contributor.authorPITON, Amélie
dc.contributor.authorAIT-YAHYA, Emilie
dc.contributor.authorGHOUMID, Jamal
dc.contributor.authorSMOL, Thomas
dc.date.accessioned2025-01-31T14:39:15Z
dc.date.available2025-01-31T14:39:15Z
dc.date.issued2024-08-24
dc.identifier.issn1468-6244en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204691
dc.description.abstractEnPathogenic variants in the gene are associated with the autosomal dominant syndrome, which is characterised by global developmental delay and cardiac malformations. We investigated two heterozygous variants located at the canonical donor splice site motif of exon 7: c.1009+1G>C and c.1009+5G>C. We report that in silico predictions suggested two possible outcomes: exon 7 skipping, resulting in loss of the phosphodegron motif essential for regulation, or activation of a cryptic donor site in intron 7, leading to intron retention. RNA analysis confirmed that both variants affected the exon 7 splice donor site, resulting in the retention of 73 bp of intron 7. This retention caused a frameshift and premature translation termination, consistent with haploinsufficiency. Our results highlight the importance of combining predictive and experimental approaches to understand the functional impact of splice site variants. These insights into the molecular consequences of variants provide a deeper understanding of the genetic basis of syndrome.
dc.language.isoENen_US
dc.subject.enRNA Splicing
dc.subject.enSequence Analysis
dc.subject.enDNA
dc.subject.enRNA
dc.title.enSplice site variants in the canonical donor site of exon 7 lead to intron retention in patients with syndrome.
dc.title.alternativeJ Med Geneten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1136/jmg-2024-110154en_US
dc.subject.halSciences du Vivant [q-bio]/Génétiqueen_US
dc.identifier.pubmed39181712en_US
bordeaux.journalJournal of Medical Geneticsen_US
bordeaux.page1040-1044en_US
bordeaux.volume61en_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
bordeaux.import.sourcepubmed
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccCC BY-NC-NDen_US
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