Molecular Genetic Diagnosis with Targeted Next Generation Sequencing in a Cohort of Turkish Osteogenesis Imperfecta Patients and their Genotype-phenotype Correlation

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dc.authorid0000-0001-7037-2713
dc.authorid0000-0001-6108-0591
dc.authorid0000-0002-5220-5652
dc.authorid0000-0002-1142-3872
dc.authorid0000-0002-0584-8866
dc.authorid0000-0001-7542-7787
dc.contributor.authorOzen, Samim
dc.contributor.authorGoksen, Damla
dc.contributor.authorEvin, Ferda
dc.contributor.authorIsik, Esra
dc.contributor.authorOnay, Huseyin
dc.contributor.authorAkgun, Bilcag
dc.contributor.authorAta, Aysun
dc.contributor.authorAtik, Tahir
dc.contributor.authorOzkinay, Ferda
dc.contributor.authorDarcan, Sukran
dc.contributor.authorCogulu, Ozgur
dc.date.accessioned2025-03-05T07:48:38Z
dc.date.available2025-03-05T07:48:38Z
dc.date.issued2024
dc.departmentEge Üniversitesi, Tıp Fakültesi, Dahili Bilimler Bölümü, Çocuk Sağlığı ve Hastalıkları Ana Bilim Dalı
dc.description.abstractObjective: Osteogenesis imperfecta (OI) consists of a group of phenotypically and genetically heterogeneous connective tissue disorders that share similar skeletal anomalies causing bone fragility and deformation. The aim was to investigate the molecular genetic etiology and determine the relationship between genotype and phenotype in OI patients using targeted next-generation sequencing (NGS). Methods: A targeted NGS analysis panel (Illumina TruSight One) containing genes involved in collagen/bone synthesis was performed on the Illumina Nextseq550 platform in patients with a confirmed diagnosis of OI. Results: Fifty-six patients (female/male: 25/31) from 46 different families were included. Consanguinity was noted in 15 (32.6%) families. Based on Sillence classification 18 (33.1%) were type 1 OI, 1 (1.7%) type 2, 26 (46.4%) type 3 and 11 (19.6%) type 4. Median body weight was -1.1 (-6.8, - 2.5) standard deviation scores (SDS), and height was -2.3 (-7.6, - 1.2) SDS. Bone deformity affected 30 dentinogenesis imperfecta (DI), and 2 (3.6%) had hearing loss. Disease-causing variants in COL1A1 and COL1A2 were found in 24 (52.1%) and 6 (13%) families, respectively. In 8 (17.3%) of the remaining 16 (34.7%) families, the NGS panel revealed disease-causing variants in three different genes ( FKBP10, SERPINF1, and P3H1). Nine (23.6%) of the variants detected by NGS panel had not previously been reported and were also classified as pathogenic based on American College of Medical Genetics guidelines pathogenity scores. In ten (21.7%) families, a disease-related variant was not found in any of the 13 OI genes on the panel. Conclusion: Genetic etiology was found in 38 (82.6%) of 46 families by targeted NGS analysis. Furthermore, nine new variants were identified in known OI genes which were classified as pathogenic by standard guidelines.
dc.identifier.citationOzen, S., Goksen, D., Evin, F., Isik, E., Onay, H., Akgun, B., Ata, A., Atik, T., Duzcan, F., Ozkinay, F., Darcan, S., & Cogulu, O. (2024). Molecular genetic diagnosis with targeted next generation sequencing in a cohort of turkish osteogenesis imperfecta patients and their genotype-phenotype correlation. Journal of Clinical Research in Pediatric Endocrinology, 16(4), 431-442.
dc.identifier.doi10.4274/jcrpe.galenos.2024.2022-12-8
dc.identifier.endpage442
dc.identifier.issn1308-5727
dc.identifier.issue4
dc.identifier.pmid38828893
dc.identifier.scopus2-s2.0-85211930398
dc.identifier.scopusqualityQ2
dc.identifier.startpage431
dc.identifier.urihttps://doi.org/10.4274/jcrpe.galenos.2024.2022-12-8
dc.identifier.urihttps://hdl.handle.net/11454/116445
dc.identifier.volume16
dc.identifier.wosWOS:001411434400005
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorOzen, Samim
dc.institutionauthorGoksen, Damla
dc.institutionauthorIsik, Esra
dc.institutionauthorOnay, Huseyin
dc.institutionauthorAkgun, Bilcag
dc.institutionauthorAta, Aysun
dc.institutionauthorAtik, Tahir
dc.institutionauthorOzkinay, Ferda
dc.institutionauthorDarcan, Sukran
dc.institutionauthorCogulu, Ozgur
dc.institutionauthorid0000-0001-7037-2713
dc.institutionauthorid0000-0001-6108-0591
dc.institutionauthorid0000-0002-0584-8866
dc.institutionauthorid0000-0002-5220-5652
dc.institutionauthorid0000-0002-1142-3872
dc.institutionauthorid0000-0001-7542-7787
dc.language.isoen
dc.publisherGalenos Publishing House
dc.relation.ispartofJournal of Clinical Research ın Pediatric Endocrinology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCOL1A1
dc.subjectgenetics
dc.subjectnext-generation sequencing
dc.subjectOsteogenesis imperfecta
dc.titleMolecular Genetic Diagnosis with Targeted Next Generation Sequencing in a Cohort of Turkish Osteogenesis Imperfecta Patients and their Genotype-phenotype Correlation
dc.typeArticle

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