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. 2024 Dec 4;16(4):431-442.
doi: 10.4274/jcrpe.galenos.2024.2022-12-8. Epub 2024 Jun 3.

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

Samim Özen  1 , Damla Gökşen  1 , Ferda Evin  2 , Esra Işık  3 , Hüseyin Onay  4 , Bilçağ Akgün  4 , Aysun Ata  1 , Tahir Atik  3 , Füsun Düzcan  5 , Ferda Özkınay  3 , Şükran Darcan  1 , Özgür Çoğulu  3
Affiliations

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

Samim Özen et al. J Clin Res Pediatr Endocrinol. .

Abstract

Objective: 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 (53.5%), while 31 (55.4%) were evaluated as mobile. Thirty-six (60.7%) had blue sclera, 13 (23.2%) had scoliosis, 12 (21.4%) had 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.

Keywords: COL1A1; Osteogenesis imperfecta; genetics; next-generation sequencing.

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Conflict of interest statement

Conflict of Interest: Two authors of this article, Samim Özen and Damla Gökşen, are a member of the Editorial Board of the Journal of Clinical Research in Pediatric Endocrinology. However, they were not involved in any stage of the editorial decision of the manuscript. The editors who evaluated this manuscript are from different institutions. The other authors declared no conflict of interest.

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References

    1. Forlino A, Cabral WA, Barnes AM, Marini JC. New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011;7(9):540–557. doi: 10.1038/nrendo.2011.81. - DOI - PMC - PubMed
    1. Rossi V, Lee B, Marom R. Osteogenesis imperfecta: advancements in genetics and treatment. Curr Opin Pediatr. 2019;31(6):708–715. doi: 10.1097/MOP.0000000000000813. - DOI - PMC - PubMed
    1. Palomo T, Vilaça T, Lazaretti-Castro M. Osteogenesis imperfecta: diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes. 2017;24(6):381–388. doi: 10.1097/MED.0000000000000367. - DOI - PubMed
    1. Erbaş İM, İlgün Gürel D, Manav Kabayeğit Z, Koç A, Ünüvar T, Abacı A, Böber E, Anık A. Clinical, genetic characteristics and treatment outcomes of children and adolescents with osteogenesis imperfecta: a two-center experience. Connect Tissue Res. 2022;63(4):349–358. doi: 10.1080/03008207.2021.1932853. - DOI - PubMed
    1. Gupta N, Gregory SW, Deyle DR, Tebben PJ. Three Patient Kindred with a Novel Phenotype of Osteogenesis Imperfecta due to a COL1A1 Variant. J Clin Res Pediatr Endocrinol. 2021;13(2):218–224. doi: 10.4274/jcrpe.galenos.2020.2020.0012. - DOI - PMC - PubMed

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