{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:09:28Z","timestamp":1790611768764,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Osteogenesis imperfecta (OI) is a rare genetic disorder of the connective tissue. It presents with a wide spectrum of skeletal and extraskeletal features, and ranges in severity from mild to perinatal lethal. The disease is characterized by a heterogeneous genetic background, where approximately 85%\u201390% of cases have dominantly inherited heterozygous pathogenic variants located in the <jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic> genes. This paper presents the results of the first nationwide study, performed on a large cohort of 197 Polish OI patients. Variants were identified using a next-generation sequencing (NGS) custom gene panel and multiplex ligation probe amplification (MLPA) assay. The following OI types were observed: 1 (42%), 2 (3%), 3 (35%), and 4 (20%). Collagen type I pathogenic variants were reported in 108 families. Alterations were observed in \u03b11 and \u03b12 in 70% and 30% of cases, respectively. The presented paper reports 97 distinct causative variants and expands the OI database with 38 novel pathogenic changes. It also enabled the identification of the first glycine-to-tryptophan substitution in the <jats:italic>COL1A1<\/jats:italic> gene and brought new insights into the clinical severity associated with variants localized in \u201clethal regions\u201d. Our results contribute to a better understanding of the clinical and genetic aspects of OI.<\/jats:p>","DOI":"10.3389\/fendo.2023.1149982","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T10:57:52Z","timestamp":1695380272000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["NGS analysis of collagen type I genes in Polish patients with Osteogenesis imperfecta: a nationwide multicenter study"],"prefix":"10.3389","volume":"14","author":[{"given":"Kinga","family":"Sa\u0142aci\u0144ska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Pinkier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Rutkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Chlebna-Sok\u00f3\u0142","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Jakubowska-Pietkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Micha\u0142us","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"K\u0119pczy\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Salachna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Wieczorek-Cichecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Piotrowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Chilarska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Jamsheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Matusik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Wilk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Petriczko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Gi\u017cewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Stecewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczys\u0142aw","family":"Walczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Rybak-Krzyszkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Lewi\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Gach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis imperfecta","volume":"387","author":"Forlino","year":"2016","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181a1ff7b","article-title":"Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition","volume":"11","author":"Basel","year":"2009","journal-title":"Genet Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61366","article-title":"Nosology and classification of genetic skeletal disorders: 2019 revision","volume":"179","author":"Mortier","year":"2019","journal-title":"Am J Med Genet A."},{"key":"B4","first-page":"1993","article-title":"COL1A1\/2 osteogenesis imperfecta","volume-title":"GeneReviews","author":"Steiner","year":"2021"},{"key":"B5","unstructured":"OMIM database"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36545","article-title":"Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment","author":"Van Dijk","year":"2014","journal-title":"Am J Med Genet A."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3723-3","article-title":"Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment","volume":"27","author":"Trejo","year":"2016","journal-title":"Osteoporos Int"},{"key":"B8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.trsl.2016.11.005","article-title":"Osteogenesis imperfecta: new genes reveal novel mechanisms in bone dysplasia","volume":"181","author":"Kang","year":"2017","journal-title":"Transl Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.692978","article-title":"Novel mutations within collagen Alpha1(I) and Alpha2(I) ligand-binding sites, broadening the spectrum of osteogenesis imperfecta - current insights into collagen type I lethal regions","volume":"12","author":"Sa\u0142aci\u0144ska","year":"2021","journal-title":"Front Genet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1996","article-title":"The first glycine-to-tryptophan substitution in the COL1A1 gene identified in a patient with progressively-deforming Osteogenesis imperfecta","volume":"10","author":"Sa\u0142aci\u0144ska","year":"2022","journal-title":"Mol Genet Genomic Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/s0945-053x(98)90109-3","article-title":"An alpha2(I) glycine to aspartate substitution is responsible for the presence of a kink in type I collagen in a lethal case of osteogenesis imperfecta","volume":"17","author":"Forlino","year":"1998","journal-title":"Matrix Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00722","article-title":"COL1A1\/2 pathogenic variants and phenotype characteristics in ukrainian osteogenesis imperfecta patients","volume":"10","author":"Zhytnik","year":"2019","journal-title":"Front Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.4.284","article-title":"Perinatal lethal osteogenesis imperfecta","volume":"32","author":"Cole","year":"1995","journal-title":"J Med Genet"},{"key":"B14","volume-title":"OIVD database","year":""},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.5604\/08606196.1222458","article-title":"Diversity of clinical symptoms of osteogenesis imperfecta in children \u2013 diagnostic difficulties based on own experience","author":"Rusi\u0144ska","year":"2016","journal-title":"Post N Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0373-x","article-title":"Genotype-phenotype correlation study in 364 osteogenesis imperfecta Italian patients","volume":"27","author":"Maioli","year":"2019","journal-title":"Eur J Hum Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1038\/ejhg.2015.129","article-title":"Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta","volume":"23","author":"Lindahl","year":"2015","journal-title":"Eur J Hum Genet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20071","article-title":"Lack of correlation between the type of COL1A1 or COL1A2 mutation and hearing loss in osteogenesis imperfecta patients","volume":"24","author":"Hartikka","year":"2004","journal-title":"Hum Mutat"},{"key":"B19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40246-017-0115-5","article-title":"Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients","volume":"11","author":"Zhytnik","year":"2017","journal-title":"Hum Genomics"},{"key":"B20","article-title":"III: Clinical and molecular genetics of Osteogenesis imperfecta, Chapter 10: Osteogenesis Imperfecta Genotypes and Genotype\u2013Phenotype Relationships","volume-title":"Osteogenesis imperfecta - A translational approach to brittle bone disease","author":"Dalgleish","year":"2014"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1505","article-title":"New genes in bone development: what\u2019s new in osteogenesis imperfecta","volume":"98","author":"Marini","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22812","article-title":"Molecular outcome, prediction, and clinical consequences of splice variants in COL1A1, which encodes the pro\u03b11(I) chains of type I procollagen","volume":"36","author":"Schleit","year":"2015","journal-title":"Hum Mutat"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1021\/bi800026k","article-title":"Predicting the clinical lethality of osteogenesis imperfecta from collagen glycine mutations","volume":"47","author":"Bodian","year":"2008","journal-title":"Biochemistry"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.7.433","article-title":"Osteogenesis imperfecta: translation of mutation to phenotype","volume":"28","author":"Byers","year":"1991","journal-title":"J Med Genet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn374","article-title":"Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype-phenotype relationships","volume":"18","author":"Bodian","year":"2009","journal-title":"Hum Mol Genet"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22677","article-title":"Type I procollagen C-propeptide defects: study of genotype-phenotype correlation and predictive role of crystal structure","volume":"35","author":"Symoens","year":"2014","journal-title":"Hum Mutat"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20429","article-title":"Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans","volume":"28","author":"Marini","year":"2007","journal-title":"Hum Mutat"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/540178","article-title":"Genotype-phenotype correlations in autosomal dominant osteogenesis imperfecta","volume":"2011","author":"Ben Amor","year":"2011","journal-title":"J Osteoporos."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31459","article-title":"What every clinical geneticist should know about testing for osteogenesis imperfecta in suspected child abuse cases","volume":"169","author":"Pepin","year":"2015","journal-title":"Am J Med Genet C Semin Med Genet"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1149982\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T10:57:57Z","timestamp":1695380277000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1149982\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,22]]},"references-count":29,"alternative-id":["10.3389\/fendo.2023.1149982"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1149982","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,22]]},"article-number":"1149982"}}