A Novel Molecular Indicator for Inhibitor Development in Haemophilia A

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dc.authoridAkgun, Bilcag/0000-0002-5220-5652
dc.authorwosidAtik, Tahir/AAY-5682-2021
dc.authorwosidKOSE, Timur/ABH-3197-2021
dc.contributor.authorIsik, Esra
dc.contributor.authorMehdiyeva, Humay
dc.contributor.authorAkgun, Bilcag
dc.contributor.authorKose, Timur
dc.contributor.authorKavakli, Kaan
dc.contributor.authorOzkinay, Ferda
dc.contributor.authorAtik, Tahir
dc.date.accessioned2023-01-12T20:16:40Z
dc.date.available2023-01-12T20:16:40Z
dc.date.issued2021
dc.departmentN/A/Departmenten_US
dc.description.abstractAim: Previous studies have reported inhibitor development (ID) risk in those patients who have hemophilia A (HA) with missense mutations to be 3-10%. We investigated the association between ID risk and various features of missense mutations; including the impact directly related to amino acid group change. Materials and Methods: Missense mutations in the F8 gene, clinical findings of the patients including severity of HA, and ID status were obtained from the F8 gene variant database (http://www.factorviii-db.org/). Twenty amino acids were then classified into groups according to their side chains. All information regarding each specific mutation, as well as any impact of the mutation on the amino acid group change, was recorded. Additionally, localization (at which domain) of any changed amino acid in the F8 protein was noted. Combined Annotation Dependent Depletion (CADD), Rare Exome Variant Ensemble Learner (REVEL), Mendelian Clinically Applicable Pathogenicity and Deleterious Annotation using Neural Networks scores were applied to identify a significant cut-off value indicative of ID. Results: Three variations were identified that could be considered as useful in the prediction of ID in mild HA. The first being that among mild HA patients, 7.9% (n=70/883) with mutations causing no amino acid group changes showed ID. This rate, however, was only 2.9% in patients with mutations leading to amino acid group changes. Secondly; in patients with mutations causing no amino acid group changes affecting A2, A3 and C2 domains, ID risk was found to be higher than in patients with mutations leading to amino acid group changes. Thirdly; an association between ID and CADD and REVEL scores was observed. Conclusion: In mild HA patients, the characteristics of missense mutations in terms of amino acid group changes, and CADD and REVEL scores could be of considerable utility in the prediction of ID risk.en_US
dc.identifier.doi10.4274/jpr.galenos.2020.59354
dc.identifier.endpage109en_US
dc.identifier.issn2147-9445
dc.identifier.issue2en_US
dc.identifier.startpage102en_US
dc.identifier.trdizinid516396en_US
dc.identifier.urihttps://doi.org/10.4274/jpr.galenos.2020.59354
dc.identifier.urihttps://search.trdizin.gov.tr/yayin/detay/516396
dc.identifier.urihttps://hdl.handle.net/11454/78753
dc.identifier.volume8en_US
dc.identifier.wosWOS:000656055300002en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakTR-Dizinen_US
dc.language.isoenen_US
dc.publisherGalenos Yayinciliken_US
dc.relation.ispartofJournal Of Pediatric Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectHemophilia Aen_US
dc.subjectinhibitoren_US
dc.subjectF8 geneen_US
dc.subjectmutationen_US
dc.subjectmissenseen_US
dc.subjectinterpretationen_US
dc.subjectFactor-Viii Inhibitorsen_US
dc.subjectRisk-Factorsen_US
dc.subjectMilden_US
dc.subjectPathogenicityen_US
dc.subjectMutationen_US
dc.titleA Novel Molecular Indicator for Inhibitor Development in Haemophilia Aen_US
dc.typeArticleen_US

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