{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:35:48Z","timestamp":1790847348116,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"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. Genet."],"abstract":"<jats:p>Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility and abnormal connective tissue. Ninety percent of OI patients are caused by two mutations of <jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic>, and more investigation was needed to better understand the rare types of OI. We followed up 29 patients with rare types of OI for an average of 5.4 years, and genotype, height, bone mineral density (BMD), blood biochemical indexes, misdiagnosis, and fracture were recorded. <jats:italic>IFITM5<\/jats:italic> gene mutation was found in 18 patients (62.1%), which represents the most common pathogenic gene of rare types of OI in Chinese population. Thirteen cases had once been misdiagnosed, and the initial misdiagnosis rate was 44.8% (13\/29). The higher misdiagnosis rate should be paid attention to by clinicians and healthcare providers, and we also give corresponding suggestions. Compared with the non-bisphosphonate treatment group, patients treated with bisphosphonates had higher lumbar spine BMD, fewer fractures, and lower levels of \u03b2-CTX and osteocalcin. However, there was no significant difference between OI type V patients and non-type V patients. Our study enriched the knowledge of genotype and phenotype characteristics of OI patients with rare types and bisphosphonate therapy.<\/jats:p>","DOI":"10.3389\/fgene.2021.622078","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T11:27:07Z","timestamp":1626434827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Genotypic and Phenotypic Characteristics of 29 Patients With Rare Types of Osteogenesis Imperfecta: Average 5 Years of Follow-Up"],"prefix":"10.3389","volume":"12","author":[{"given":"Lei","family":"Xi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"375","DOI":"10.3389\/fendo.2019.00375","article-title":"Expanding the Clinical Spectrum of Osteogenesis Imperfecta Type V: 13 Additional Patients and Review.","volume":"10","author":"Cao","year":"","journal-title":"Front. Endocrinol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"230","DOI":"10.4158\/EP-2018-0443","article-title":"NOVEL MUTATIONS IN THE WNT1, TMEM38B, P4HB, AND PLS3 GENES IN FOUR UNRELATED CHINESE FAMILIES WITH OSTEOGENESIS IMPERFECTA.","volume":"25","author":"Cao","year":"","journal-title":"Endocr. Pract."},{"key":"B3","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/nrendo.2011.81","article-title":"New perspectives on osteogenesis imperfecta.","volume":"7","author":"Forlino","year":"2011","journal-title":"Nat. Rev. Endocrinol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.ajhg.2015.01.002","article-title":"Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta.","volume":"96","author":"Garbes","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1002\/jbmr.5650080915","article-title":"Vertebral fracture assessment using a semiquantitative technique.","volume":"8","author":"Genant","year":"1993","journal-title":"J. Bone Miner. Res."},{"key":"B6","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."},{"key":"B7","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.bone.2006.10.010","article-title":"Osteogenesis imperfecta type VI in childhood and adolescence: effects of cyclical intravenous pamidronate treatment.","volume":"40","author":"Land","year":"2007","journal-title":"Bone"},{"key":"B8","first-page":"487","article-title":"[Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years].","volume":"47","author":"Li","year":"2009","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B9","doi-asserted-by":"publisher","first-page":"984","DOI":"10.3389\/fgene.2020.00984","article-title":"Genotypic and Phenotypic Analysis in Chinese Cohort With Autosomal Recessive Osteogenesis Imperfecta.","volume":"11","author":"Li","year":"2020","journal-title":"Front. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta.","volume":"3","author":"Marini","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B11","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1016\/j.ajhg.2019.08.008","article-title":"Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta.","volume":"105","author":"Moosa","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2393","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":"B13","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1136\/jmg.23.4.328","article-title":"The birth prevalence rates for the skeletal dysplasias.","volume":"23","author":"Orioli","year":"1986","journal-title":"J. Med. Genet."},{"key":"B14","first-page":"393","article-title":"Osteogenesis imperfecta at the beginning of bone and joint decade.","volume":"42","author":"Primorac","year":"2001","journal-title":"Croat. Med. J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1007\/s13312-016-0830-3","article-title":"Worsening of Callus Hyperplasia after Bisphosphonate Treatment in Type V Osteogenesis Imperfecta.","volume":"53","author":"Ranganath","year":"2016","journal-title":"Indian Pediatr."},{"key":"B16","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ajhg.2014.12.027","article-title":"Cole-Carpenter syndrome is caused by a heterozygous missense mutation in P4HB.","volume":"96","author":"Rauch","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1016\/S0140-6736(04)16051-0","article-title":"Osteogenesis imperfecta.","volume":"363","author":"Rauch","year":"2004","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.bone.2016.02.018","article-title":"Scoliosis in osteogenesis imperfecta caused by COL1A1\/COL1A2 mutations - genotype-phenotype correlations and effect of bisphosphonate treatment.","volume":"86","author":"Sato","year":"2016","journal-title":"Bone"},{"key":"B19","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.ajhg.2012.06.011","article-title":"A mutation in the 5\u2019-UTR of IFITM5 creates an in-frame start codon and causes autosomal-dominant osteogenesis imperfecta type V with hyperplastic callus.","volume":"91","author":"Semler","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/s0140-6736(78)90763-8","article-title":"Classification of osteogenesis imperfect.","volume":"1","author":"Sillence","year":"1978","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1111\/j.1399-0004.1989.tb02912.x","article-title":"Birth prevalence rates of skeletal dysplasias.","volume":"35","author":"Stoll","year":"1989","journal-title":"Clin. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/s0140-6736(86)91609-0","article-title":"Osteogenesis imperfecta is linked to both type I collagen structural genes.","volume":"2","author":"Sykes","year":"1986","journal-title":"Lancet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1007\/s00774-006-0737-5","article-title":"Establishment of peak bone mineral density in Southern Chinese males and its comparisons with other males from different regions of China.","volume":"25","author":"Tan","year":"2007","journal-title":"J. Bone Miner. Metab."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1007\/s00198-017-4141-x","article-title":"Long-term follow-up in osteogenesis imperfecta type VI.","volume":"28","author":"Trejo","year":"2017","journal-title":"Osteoporos. Int."},{"key":"B25","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1007\/s00774-020-01163-5","article-title":"Clinical and genetic analysis in 185 Chinese probands of osteogenesis imperfecta.","volume":"39","author":"Xi","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e82098","DOI":"10.1371\/journal.pone.0082098","article-title":"Bone mineral density of the spine in 11,898 Chinese infants and young children: a cross-sectional study.","volume":"8","author":"Xu","year":"2013","journal-title":"PLoS One"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3662","DOI":"10.3892\/ijmm.2018.3542","article-title":"Novel mutations of the SERPINF1 and FKBP10 genes in Chinese families with autosomal recessive osteogenesis imperfecta.","volume":"41","author":"Zhang","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1007\/s00198-016-3866-2","article-title":"Novel mutations in the SEC24D gene in Chinese families with autosomal recessive osteogenesis imperfecta.","volume":"28","author":"Zhang","year":"2017","journal-title":"Osteoporos. Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"4918","DOI":"10.3892\/mmr.2016.5835","article-title":"Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta.","volume":"14","author":"Zhang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e72337","DOI":"10.1371\/journal.pone.0072337","article-title":"Phenotype and genotype analysis of Chinese patients with osteogenesis imperfecta type V.","volume":"8","author":"Zhang","year":"2013","journal-title":"PLoS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00774-011-0284-6","article-title":"The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta.","volume":"30","author":"Zhang","year":"2012","journal-title":"J. Bone Miner. Metab."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e107594","DOI":"10.1371\/journal.pone.0107594","article-title":"Novel mutations in FKBP10 and PLOD2 cause rare Bruck syndrome in Chinese patients.","volume":"9","author":"Zhou","year":"2014","journal-title":"PLoS One"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.622078\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T11:27:09Z","timestamp":1626434829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2021.622078\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":32,"alternative-id":["10.3389\/fgene.2021.622078"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2021.622078","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,16]]},"article-number":"622078"}}