Biallelic Novel USP53 Splicing Variant Disrupting the Gene Function that Causes Cholestasis Phenotype and Review of the Literature

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dc.contributor.authorGezdirici, Alper
dc.contributor.authorSengul, Ozlem Kalaycik
dc.contributor.authorDogan, Mustafa
dc.contributor.authorOzguven, Banu Y.
dc.contributor.authorAkbulut, Ekrem
dc.date.accessioned2026-06-19T06:38:22Z
dc.date.available2026-06-19T06:38:22Z
dc.date.issued2023
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractIntroduction: Hereditary cholestasis is a heterogeneous group of liver diseases that mostly show autosomal recessive inheritance. The phenotype of cholestasis is highly variable. Molecular genetic testing offers an useful approach to differentiate different types of cholestasis because some symptoms and findings overlap. Biallelic variants in USP53 have recently been reported in cholestasis phenotype. Methods: In this study, we aimed to characterize clinical findings and biological insights on a novel USP53 splice variant causing cholestasis phenotype and provided a review of the literature. We performed whole-exome sequencing and then confirmed it with Sanger sequencing. In addition, as a result of in silico analyses and cDNA analysis, we showed that the USP53 protein in our patient was shortened. Results: We report a novel splice variant (NM_019050.2:c.238-1G>C) in the USP53 gene via whole-exome sequencing in a patient with cholestasis phenotype. This variant was confirmed by Sanger sequencing and was a result of family segregation analysis; it was found to be in a heterozygous state in the parents and the other healthy elder brother of our patient. According to in silico analyses, the change in the splice region resulted in an increase in the length of exon 2, whereas the stop codon after the additional 3 amino acids (VTF) caused the protein to terminate prematurely. Thus, the mature USP53 protein, consisting of 1,073 amino acids, has been reduced to a small protein of 82 amino acids. Conclusion: We propose a model for the tertiary structure of USP53 for the first time, and together with all these data, we support the association of biallelic variants of the USP53 gene with cholestasis phenotype. We also present a comparison of previously reported patients with USP53-associated cholestasis phenotype to contribute to the literature.
dc.identifier.doi10.1159/000523937
dc.identifier.endpage484
dc.identifier.issn1661-8769
dc.identifier.issn1661-8777
dc.identifier.issue6
dc.identifier.orcid0000-0003-0464-6565
dc.identifier.orcid0000-0002-7526-9835
dc.identifier.pmid36660033
dc.identifier.scopus2-s2.0-85130458659
dc.identifier.scopusqualityQ4
dc.identifier.startpage471
dc.identifier.urihttps://doi.org/10.1159/000523937
dc.identifier.urihttps://hdl.handle.net/20.500.12899/5528
dc.identifier.volume13
dc.identifier.wosWOS:000793484900001
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherKarger
dc.relation.ispartofMolecular Syndromology
dc.relation.publicationcategoryDiğer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260612
dc.subjectUsp53
dc.subjectCholestasis
dc.subjectHomology Modeling
dc.subjectWhole-Exome Sequencing
dc.subjectGenotype-Phenotype Correlation
dc.titleBiallelic Novel USP53 Splicing Variant Disrupting the Gene Function that Causes Cholestasis Phenotype and Review of the Literature
dc.typeReview

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