{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:35:43Z","timestamp":1788820543747,"version":"build-2803163510"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Child Health Research Institute at Children\u2019s Nebraska"},{"DOI":"10.13039\/100006518","name":"University of Nebraska Medical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006518","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility with extraskeletal manifestations mostly due to COL1A1 and COL1A2 variants. Currently, 23 genes have been implicated in the pathogenesis of OI; however, literature on genotype\u2013phenotype correlation and incidence of non-skeletal clinical features are limited. This study aims to identify genotype\u2013phenotype correlations in patients with OI, allowing clinicians to better inform families of prognosis, optimize patient care, and facilitate evidence-based clinical decision-making. We retrospectively reviewed 294 patients with OI to collect demographic data, clinical characteristics, and genotypic information. Patients were stratified by COL1A1\/1A2 vs non-COL1A1\/1A2 variants to evaluate differences in phenotype. The majority of OI was due to variants in COL1A1\/1A2 (91%), with the remaining 9% due to non-COL1A1\/1A2 variants. Most patients in the COL1A1\/2 group were White compared to the non-COL1A1\/2 group (78% vs 50%; p\u2009=\u20090.004). COL1A\/1A2 patients had higher incidence of blue sclerae (83% vs 58%, p\u2009=\u20090.002), dentinogenesis imperfecta (49% vs 15%, p\u2009&amp;lt;\u20090.001), and family history of OI (34% vs 12%, p\u2009=\u20090.03). Those in the non-COL1A1\/1A2 group have higher rates of scoliosis compared to those in the COL1A1\/1A2 group (62% vs 40%, p\u2009=\u20090.04), as well as higher rates of expressive language disorder\/delay (15% vs 0.4% in non-COL1A1\/1A2 and COL1A1\/1A2 patients, respectively; p\u2009&amp;lt;\u20090.001). Identifying the underlying molecular etiology early is imperative for optimal clinical care, allowing for appropriate risk counseling, identification of affected relatives, and improved anticipatory care and management. These data support that rare subtypes of OI occur more frequently in non-White individuals and demonstrated genetic associations with incidence of blue sclera, dentinogenesis imperfecta, scoliosis, and expressive language disorders.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziae125","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T17:38:55Z","timestamp":1727717935000},"source":"Crossref","is-referenced-by-count":9,"title":["Genotype\u2013phenotype correlations in 294 pediatric patients with osteogenesis imperfecta"],"prefix":"10.1093","volume":"8","author":[{"given":"Jay J","family":"Byrd","sequence":"first","affiliation":[{"name":"College of Medicine, University of Nebraska Medical Center , Omaha, NE, 68198,","place":["United States"]},{"name":"The Child Health Research Institute, University of Nebraska Medical Center , Omaha, NE, 68198,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C","family":"White","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Nebraska Medical Center , Omaha, NE, 68198,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire G","family":"Nissen","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Nebraska Medical Center , Omaha, NE, 68198,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makayla","family":"Schissel","sequence":"additional","affiliation":[{"name":"Department of Biostatistics , College of Public Health, , Omaha, NE, 68198,","place":["United States"]},{"name":"University of Nebraska Medical Center , College of Public Health, , Omaha, NE, 68198,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Van Ormer","sequence":"additional","affiliation":[{"name":"The Child Health Research Institute, University of Nebraska Medical Center , Omaha, NE, 68198,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danita","family":"Velasco","sequence":"additional","affiliation":[{"name":"Children\u2019s Nebraska , Department of Pediatrics, Division of Genetics Omaha, NE, 68114,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6278-9412","authenticated-orcid":false,"given":"Maegen","family":"Wallace","sequence":"additional","affiliation":[{"name":"Phoenix Childrens Hospital , Department of Pediatric Orthopaedic Surgery Phoenix, AZ, 85016,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"issue":"1","key":"2024102412152889700_ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat Rev Dis Prim"},{"issue":"1","key":"2024102412152889700_ref2","doi-asserted-by":"publisher","first-page":"22","DOI":"10.6065\/apem.2142144.072","article-title":"Genotype-phenotype correlations and long-term efficacy of pamidronate therapy in patients with osteogenesis imperfecta","volume":"27","author":"Choi","year":"2022","journal-title":"Ann Pediatr Endocrinol Metab"},{"issue":"26","key":"2024102412152889700_ref3","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1056\/NEJMoa063804","article-title":"Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta","volume":"355","author":"Barnes","year":"2006","journal-title":"N Engl J Med"},{"issue":"2","key":"2024102412152889700_ref4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.ocl.2018.10.003","article-title":"Osteogenesis imperfecta","volume":"50","author":"Franzone","year":"2019","journal-title":"Orthop Clin N Am"},{"issue":"2","key":"2024102412152889700_ref5","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1136\/jmg.16.2.101","article-title":"Genetic heterogeneity in osteogenesis imperfecta","volume":"16","author":"Sillence","year":"1979","journal-title":"J Med Genet"},{"issue":"12","key":"2024102412152889700_ref6","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1002\/ajmg.a.37365","article-title":"Nosology and classification of genetic skeletal disorders: 2015 revision","volume":"167","author":"Bonafe","year":"2015","journal-title":"Am J Med Genet A"},{"key":"2024102412152889700_ref7","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"},{"issue":"5","key":"2024102412152889700_ref8","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1002\/ajmg.a.63132","article-title":"Nosology of genetic skeletal disorders: 2023 revision","volume":"191","author":"Unger","year":"2023","journal-title":"Am J Med Genet"},{"issue":"6","key":"2024102412152889700_ref9","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/ejhg.2009.242","article-title":"Genotype\u2013phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I","volume":"18","author":"Rauch","year":"2010","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"2024102412152889700_ref10","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1359\/jbmr.091109","article-title":"Relationship between genotype and skeletal phenotype in children and adolescents with osteogenesis imperfecta","volume":"25","author":"Rauch","year":"2010","journal-title":"J Bone Miner Res"},{"issue":"3","key":"2024102412152889700_ref11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1097\/MCD.0b013e32836032f0","article-title":"Genotype\u2013phenotype study in type V osteogenesis imperfecta","volume":"22","author":"Balasubramanian","year":"2013","journal-title":"Clin Dysmorphol"},{"issue":"8","key":"2024102412152889700_ref12","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/ejhg.2015.81","article-title":"Genetic epidemiology, prevalence, and genotype\u2013phenotype correlations in the Swedish population with osteogenesis imperfecta","volume":"23","author":"Lindahl","year":"2015","journal-title":"Eur J Hum Genet"},{"issue":"10","key":"2024102412152889700_ref13","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1007\/s00198-017-4143-8","article-title":"Gene mutation spectrum and genotype-phenotype correlation in a cohort of Chinese osteogenesis imperfecta patients revealed by targeted next generation sequencing","volume":"28","author":"Liu","year":"2017","journal-title":"Osteoporos Int"},{"key":"2024102412152889700_ref14","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.bone.2018.02.029","article-title":"Diagnostic strategies and genotype-phenotype correlation in a large Indian cohort of osteogenesis imperfecta","volume":"110","author":"Mrosk","year":"2018","journal-title":"Bone"},{"issue":"7","key":"2024102412152889700_ref15","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1038\/s41431-019-0373-x","article-title":"Genotype\u2013phenotype correlation study in 364 osteogenesis imperfecta Italian patients","volume":"27","author":"Maioli","year":"2019","journal-title":"Eur J Hum Genet"},{"issue":"6","key":"2024102412152889700_ref16","doi-asserted-by":"publisher","first-page":"e1675","DOI":"10.1002\/mgg3.1675","article-title":"Genetic analysis in Japanese patients with osteogenesis imperfecta: genotype and phenotype spectra in 96 probands","volume":"9","author":"Higuchi","year":"2021","journal-title":"Mol Genet Genomic Med"},{"issue":"8","key":"2024102412152889700_ref17","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.eprac.2022.05.003","article-title":"Genotype-phenotype relationship and follow-up analysis of a Chinese cohort with osteogenesis imperfecta","volume":"28","author":"Wei","year":"2022","journal-title":"Endocr Pract"},{"issue":"5","key":"2024102412152889700_ref18","doi-asserted-by":"publisher","first-page":"e507","DOI":"10.1097\/BPO.0000000000002116","article-title":"Does the skeletal phenotype of osteogenesis imperfecta differ for patients with non-COL1A1\/2 mutations? A retrospective study in 113 patients","volume":"42","author":"Zerfu","year":"2022","journal-title":"J Pediatr Orthop"},{"issue":"10028","key":"2024102412152889700_ref19","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis imperfecta","volume":"387","author":"Forlino","year":"2016","journal-title":"Lancet"},{"issue":"5","key":"2024102412152889700_ref20","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1136\/jmedgenet-2013-101567","article-title":"Mutations in WNT1 are a cause of osteogenesis imperfecta","volume":"50","author":"Fahiminiya","year":"2013","journal-title":"J Med Genet"},{"issue":"4","key":"2024102412152889700_ref21","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.ajhg.2013.02.010","article-title":"Mutations in WNT1 cause different forms of bone fragility","volume":"92","author":"Keupp","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"4","key":"2024102412152889700_ref22","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.ajhg.2013.02.009","article-title":"WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta","volume":"92","author":"Pyott","year":"2013","journal-title":"Am J Hum Genet"},{"issue":"6","key":"2024102412152889700_ref23","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1136\/jmedgenet-2015-103476","article-title":"Variable brain phenotype primarily affects the brainstem and cerebellum in patients with osteogenesis imperfecta caused by recessive WNT1 mutations","volume":"53","author":"Aldinger","year":"2016","journal-title":"J Med Genet"},{"issue":"5","key":"2024102412152889700_ref24","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1038\/s41436-018-0307-y","article-title":"Longitudinal growth curves for children with classical osteogenesis imperfecta (types III and IV) caused by structural pathogenic variants in type I collagen","volume":"21","author":"Barber","year":"2019","journal-title":"Genet Med"}],"container-title":["JBMR Plus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jbmrplus\/advance-article-pdf\/doi\/10.1093\/jbmrpl\/ziae125\/59460957\/ziae125.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/8\/11\/ziae125\/60011080\/ziae125.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article-pdf\/8\/11\/ziae125\/60011080\/ziae125.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T12:15:41Z","timestamp":1729772141000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmrplus\/article\/doi\/10.1093\/jbmrpl\/ziae125\/7796632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,30]]},"references-count":24,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,10,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jbmrpl\/ziae125","relation":{},"ISSN":["2473-4039"],"issn-type":[{"value":"2473-4039","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11]]},"published":{"date-parts":[[2024,9,30]]},"article-number":"ziae125"}}