{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:49:17Z","timestamp":1773269357153,"version":"3.50.1"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genome Var"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The purpose of this study was to describe a family with spondyloepiphyseal dysplasia caused by a novel type II collagen gene (<jats:italic>COL2A1<\/jats:italic>) mutation and the family\u2019s phenotypic diversity. Clinical and radiographic examinations of skeletal dysplasia were conducted on seven affected family members across two generations. The entire coding region of <jats:italic>COL2A1<\/jats:italic>, including the flanking intron regions, was analyzed with PCR and direct sequencing. The stature of the subjects ranged from extremely short to within normal height range. Hip deformity and advanced osteoarthritis were noted in all the subjects, ranging from severe coxa plana to mild acetabular dysplasia. Atlantoaxial subluxation combined with a hypoplastic odontoid process was found in three of the subjects. Various degrees of platyspondyly were confirmed in all subjects. Genetically, a novel <jats:italic>COL2A1<\/jats:italic> mutation (c.1349G&gt;C, p.Gly450Ala) was identified in all the affected family members; however, it was not present in the one unaffected family member tested. We described a family with spondyloepiphyseal dysplasia and a novel <jats:italic>COL2A1<\/jats:italic> mutation (c.1349G&gt;C, p.Gly450Ala). Phenotypes were diverse even among individuals with the same mutation and within the same family.<\/jats:p>","DOI":"10.1038\/hgv.2016.7","type":"journal-article","created":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T19:39:25Z","timestamp":1463773165000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel type II collagen gene mutation in a family with spondyloepiphyseal dysplasia and extensive intrafamilial phenotypic diversity"],"prefix":"10.1038","volume":"3","author":[{"given":"Yasuharu","family":"Nakashima","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuma","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gen","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Ikegawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihide","family":"Iwamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"BFhgv20167_CR1","first-page":"56","volume":"153","author":"J Spranger","year":"1994","unstructured":"Spranger J, Winterpacht A, Zabel B . The type II collagenopathies: a spectrum of chondrodysplasias. Eur J Pediatr 1994; 153: 56\u201365.","journal-title":"Eur J Pediatr"},{"key":"BFhgv20167_CR2","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1002\/ajmg.a.37365","volume":"167","author":"L Bonafe","year":"2015","unstructured":"Bonafe L, Cormier-Daire V, Hall C, Lachman R, Mortier G, Mundlos S et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A 2015; 167: 2869\u20132892.","journal-title":"Am J Med Genet A"},{"key":"BFhgv20167_CR3","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/humu.20179","volume":"26","author":"G Nishimura","year":"2005","unstructured":"Nishimura G, Haga N, Kitoh H, Tanaka Y, Sonoda T, Kitamura M et al. The phenotypic spectrum of COL2A1 mutations. 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Identification of three novel mutations in the COL2A1 gene in four unrelated Chinese families with spondyloepiphyseal dysplasia congenita. Biochem Biophys Res Commun 2011; 413: 504\u2013508.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFhgv20167_CR9","doi-asserted-by":"publisher","first-page":"E1461","DOI":"10.1002\/humu.21257","volume":"31","author":"AJ Richards","year":"2010","unstructured":"Richards AJ, McNinch A, Martin H, Oakhill K, Rai H, Waller S et al. Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Hum Mutat 2010; 31: E1461\u2013E1471.","journal-title":"Hum Mutat"},{"key":"BFhgv20167_CR10","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1136\/jmg.37.4.263","volume":"37","author":"GR Mortier","year":"2000","unstructured":"Mortier GR, Weis M, Nuytinck L, King LM, Wilkin DJ, De Paepe A et al. Report of five novel and one recurrent COL2A1 mutations with analysis of genotype-phenotype correlation in patients with a lethal type II collagen disorder. J Med Genet 2000; 37: 263\u2013271.","journal-title":"J Med Genet"},{"key":"BFhgv20167_CR11","doi-asserted-by":"crossref","first-page":"13663","DOI":"10.1016\/S0021-9258(17)36881-3","volume":"269","author":"P Freisinger","year":"1994","unstructured":"Freisinger P, Ala-Kokko L, LeGuellec D, Franc S, Bouvier R, Ritvaniemi P et al. Mutation in the COL2A1 gene in a patient with hypochondrogenesis. Expression of mutated COL2A1 gene is accompanied by expression of genes for type I procollagen in chondrocytes. 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