Characterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohort

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dc.authoridHiz, Ayse Semra/0000-0002-8020-4884
dc.authoridBuratti, Emanuele/0000-0002-1356-9074
dc.authorwosidBuratti, Emanuele/K-4691-2016
dc.contributor.authorSonmezler, Ece
dc.contributor.authorStuani, Cristiana
dc.contributor.authorHiz Kurul, Semra
dc.contributor.authorGungor, Serdal
dc.contributor.authorBuratti, Emanuele
dc.contributor.authorOktay, Yavuz
dc.date.accessioned2024-08-04T20:57:21Z
dc.date.available2024-08-04T20:57:21Z
dc.date.issued2024
dc.departmentİnönü Üniversitesien_US
dc.description.abstractAlthough they are rare in the population, rare neurodevelopmental disorders (RNDDs) constitute a significant portion of all rare diseases. While advancements in sequencing technologies led to improvements in diagnosing and managing rare neurodevelopmental diseases, accurate pathogenicity classification of the identified variants is still challenging. Sequence variants altering pre-mRNA splicing make up a significant part of pathogenic variants. Despite advances in the in silico prediction tools, noncanonical splice site variants are one of the groups of variants that pose a challenge in their clinical interpretation. In this study, we analyzed the effects of seven splicing variants we had previously proposed as disease-causing and demonstrated that all but one of the seven variants had a strong or moderate effect on splicing, as assessed by a minigene assay. Next, applying U1 snRNAs engineered for different splicing variants in the corresponding genes and expressed with minigene plasmids in HeLa cells provided a partial correction in four of the studied genes to varying degrees. Findings from our study highlight the importance of in vitro minigene-based assays for the reclassification of putative splice-altering variants of uncertain significance and the therapeutic potential of modified U1 snRNAs in RNDDs.en_US
dc.description.sponsorshipAriSLA [216S771]; TUBITAK-Katip Celebi-Newton Fund [9719]; European Molecular Biology Organization (EMBO); AriSLA (Italy) project NOSRESCUEALS [216S771, 9719]en_US
dc.description.sponsorshipWe would like to acknowledge the group of patients and their families for participating in the CONSEQUITUR Project (216S771) funded by the TUBITAK-Katip Celebi-Newton Fund. We also would like to thank the European Molecular Biology Organization (EMBO) for supporting ES with the Scientific Exchange Grant 9719. EB is funded by AriSLA (Italy) project NOSRESCUEALS. ES was supported by EMBO Scientific Exchange Grant #9719. SHK and YO were funded by TUBITAK-Katip Celebi-Newton Fund Project (216S771).en_US
dc.identifier.doi10.1155/2024/7760556
dc.identifier.issn1059-7794
dc.identifier.issn1098-1004
dc.identifier.urihttps://doi.org/10.1155/2024/7760556
dc.identifier.urihttps://hdl.handle.net/11616/102568
dc.identifier.volume2024en_US
dc.identifier.wosWOS:001248629500001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.language.isoenen_US
dc.publisherWiley-Hindawien_US
dc.relation.ispartofHuman Mutationen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectEhlers-Danlos-Syndromeen_US
dc.subjectMutationen_US
dc.subjectIdentificationen_US
dc.subjectIspden_US
dc.titleCharacterization and Engineered U1 snRNA Rescue of Splicing Variants in a Turkish Neurodevelopmental Disease Cohorten_US
dc.typeArticleen_US

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