{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:08:39Z","timestamp":1791756519031,"version":"4.3.4"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2010,5,27]],"date-time":"2010-05-27T00:00:00Z","timestamp":1274918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that in the majority of cases is caused by mutations in COL1A1 or COL1A2, the genes that encode the two collagen type I \u03b1 chains, \u03b11(I) and \u03b12(I). In this study, we examined the relationship between collagen type I mutations and bone densitometric and histomorphometric findings in pediatric OI patients who had not received bisphosphonate treatment. Lumbar spine areal bone mineral density (LS aBMD) was measured in 192 patients (99 girls, 93 boys; age range 3 weeks to 16.9 years) who had either COL1A1 mutations leading to haploinsufficiency (n\u2009=\u200952) or mutations that lead to the substitution of glycine by another amino acid in the triple-helical domain of either the \u03b11(I) (n\u2009=\u200958) or the \u03b12(I) chain (n\u2009=\u200982). Compared with patients with helical mutations, patients with COL1A1 haploinsufficiency on average were taller and heavier and had higher LS aBMD. After adjustment for age, sex, and height Z-scores, the mean LS aBMD Z-scores were \u22124.0 for the haploinsufficiency group and \u22124.7 for both helical mutation groups. In the whole patient population, the average LS aBMD Z-score was higher by 0.6 (95% confidence interval 0.2\u20131.0) in girls than in boys. Iliac bone histomorphometry (in a subgroup of 96 patients) showed that outer bone size (core width) and trabecular bone volume were similar between genotypic groups, but cortical width was 49% higher in the haploinsufficiency group compared with patients with helical mutations in \u03b12(I). Bone turnover parameters were lower in the haploinsufficiency group than in patients with helical mutations. In the group of patients with helical mutations, neither the type of \u03b1 chain affected, nor the type of amino acid substituting for glycine, nor the position of the mutation in the \u03b1 chain had a detectable relationship with LS aBMD or histomorphometric results. Thus patients with haploinsufficiency mutations had a milder skeletal phenotype than patients with mutations affecting glycine residues, but there was no clear genotype-phenotype correlation among patients with helical glycine mutations. \u00a9 2010 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1359\/jbmr.091109","type":"journal-article","created":{"date-parts":[[2009,11,24]],"date-time":"2009-11-24T03:09:45Z","timestamp":1259032185000},"page":"1367-1374","source":"Crossref","is-referenced-by-count":109,"title":["Relationship between genotype and skeletal phenotype in children and adolescents with osteogenesis imperfecta"],"prefix":"10.1093","volume":"25","author":[{"given":"Frank","family":"Rauch","sequence":"first","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liljana","family":"Lalic","sequence":"additional","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Roughley","sequence":"additional","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis H","family":"Glorieux","sequence":"additional","affiliation":[{"name":"Genetics Unit, Shriners Hospital for Children, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,27]]},"reference":[{"key":"2024020320142528400_bib1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0140-6736(04)16051-0","article-title":"Osteogenesis 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