Effectiveness of whole exome sequencing analyses in the molecular diagnosis of osteogenesis imperfecta

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dc.authoridEvin, Ferda/0000-0001-7169-890X
dc.authoridOzen, Samim/0000-0001-7037-2713
dc.authoridCOGULU, OZGUR/0000-0002-9037-5599
dc.contributor.authorEvin, Ferda
dc.contributor.authorAtik, Tahir
dc.contributor.authorOnay, Huseyin
dc.contributor.authorGoksen, Damla
dc.contributor.authorDarcan, Sukran
dc.contributor.authorCogulu, Ozgur
dc.contributor.authorOzen, Samim
dc.date.accessioned2024-08-31T07:49:56Z
dc.date.available2024-08-31T07:49:56Z
dc.date.issued2024
dc.departmentEge Üniversitesien_US
dc.description.abstractObjectives Osteogenesis imperfecta (OI) is a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. This study aimed to investigate the molecular genetic etiology and to determine the relationship between genotype and phenotype in OI patients with whole exome sequencing (WES).Methods Multiplex-Ligation dependent Probe Amplification (MLPA) analysis of COL1A1 and COL1A2 and WES were performed on cases between the ages of 0 and 18 whose genetic etiology could not be determined before using a targeted next-generation sequencing panel, including 13 genes (COL1A1, COL1A2, IFITM5, SERPINF1, CRTAP, P3H1, PPIB, SERPINH1, FKBP10, SP7, BMP1, MBTPS2, PLOD2) responsible for OI.Results Twelve patients (female/male: 4/8) from 10 different families were included in the study. In 6 (50 %) families, consanguineous marriage was noted. The clinical typing based on Sillence classification; 3 (25 %) patients were considered to be type I, 7 (58.3 %) type III, and 2 (16.7 %) type IV. Deletion/duplication wasn't detected in the COL1A1 and COL1A2 genes in the MLPA analysis of the patients. Twelve patients were molecularly analyzed by WES, and in 6 (50 %) of them, a disease-causing variant in three different genes (FKBP10, P3H1, and WNT1) was identified. Two (33.3 %) detected variants in all genes have not been previously reported in the literature and were considered deleterious based on prediction tools. In 6 cases, no variants were detected in disease-causing genes.Results Twelve patients (female/male: 4/8) from 10 different families were included in the study. In 6 (50 %) families, consanguineous marriage was noted. The clinical typing based on Sillence classification; 3 (25 %) patients were considered to be type I, 7 (58.3 %) type III, and 2 (16.7 %) type IV. Deletion/duplication wasn't detected in the COL1A1 and COL1A2 genes in the MLPA analysis of the patients. Twelve patients were molecularly analyzed by WES, and in 6 (50 %) of them, a disease-causing variant in three different genes (FKBP10, P3H1, and WNT1) was identified. Two (33.3 %) detected variants in all genes have not been previously reported in the literature and were considered deleterious based on prediction tools. In 6 cases, no variants were detected in disease-causing genes.Conclusions This study demonstrates rare OI types' clinical and molecular features; genetic etiology was determined in 6 (50 %) 12 patients with the WES analysis. In addition, two variants in OI genes have been identified, contributing to the literature.en_US
dc.description.sponsorshipEge University Scientific Research Projects [TGA-2021-22611]en_US
dc.description.sponsorshipThis project was supported by Ege University Scientific Research Projects with grant number TGA-2021-22611.en_US
dc.identifier.doi10.1515/jpem-2024-0058
dc.identifier.endpage700en_US
dc.identifier.issn0334-018X
dc.identifier.issn2191-0251
dc.identifier.issue8en_US
dc.identifier.pmid38953412en_US
dc.identifier.scopus2-s2.0-85197613100en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage693en_US
dc.identifier.urihttps://doi.org/10.1515/jpem-2024-0058
dc.identifier.urihttps://hdl.handle.net/11454/105046
dc.identifier.volume37en_US
dc.identifier.wosWOS:001260040300001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWalter De Gruyter Gmbhen_US
dc.relation.ispartofJournal of Pediatric Endocrinology & Metabolismen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240831_Uen_US
dc.subjectOsteogenesis Imperfectaen_US
dc.subjectWhole Exome Sequencingen_US
dc.subjectGeneticsen_US
dc.titleEffectiveness of whole exome sequencing analyses in the molecular diagnosis of osteogenesis imperfectaen_US
dc.typeArticleen_US

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