{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:59:59Z","timestamp":1772067599818,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,5,31]],"date-time":"2008-05-31T00:00:00Z","timestamp":1212192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify the genetic abnormality responsible for osteoarthritis (OA), avascular necrosis (AVN) of the femoral head, and Legg\u2010Calv\u00e9\u2010Perthes disease in a single family, and to determine factors responsible for the distinct phenotypes manifested by different family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty\u2010two members of a 5\u2010generation family were recruited and investigated. Diagnosis was made by independent orthopedic surgeons and radiologists. Histopathologic changes of the diseased tissue were examined. Linkage analysis was performed with markers spanning the <jats:italic>COL2A1<\/jats:italic> locus. Haplotypes were constructed and mutation of the gene was detected. Structures of the wild\u2010type and mutant proteins were modeled.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen affected members were identified (5 with isolated precocious hip OA, 6 with AVN of the femoral head, and 5 with Legg\u2010Calv\u00e9\u2010Perthes disease). A p.Gly1170Ser mutation of <jats:italic>COL2A1<\/jats:italic> cosegregated with the 3 diseases and was absent in controls. Of note, age at onset in relation to the closure status of the femoral head epiphysis was associated with the diseases, with Legg\u2010Calv\u00e9\u2010Perthes disease presenting prior to closure (at ages 6\u201314 years), AVN of the femoral head presenting during closure (at ages 15\u201318 years), and precocious OA of the hip presenting after closure (at ages 21\u201334 years). Molecular modeling predicted that the serine\u2010to\u2010glycine substitution loosens the helical structure of the protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The p.Gly1170Ser mutation of <jats:italic>COL2A1<\/jats:italic> in the family described is responsible for pathology confined to the hip joint, which presents as isolated precocious hip OA, AVN of the femoral head, or Legg\u2010Calv\u00e9\u2010Perthes disease. Age at onset in relation to closure of the femoral head epiphysis appears to be a critical factor in determining disease pattern.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23491","type":"journal-article","created":{"date-parts":[[2008,5,31]],"date-time":"2008-05-31T21:20:12Z","timestamp":1212268812000},"page":"1701-1706","source":"Crossref","is-referenced-by-count":69,"title":["Age at onset\u2013dependent presentations of premature hip osteoarthritis, avascular necrosis of the femoral head, or Legg\u2010Calv\u00e9\u2010Perthes disease in a single family, consequent upon a p.Gly1170Ser mutation of <i>COL2A1<\/i>"],"prefix":"10.1002","volume":"58","author":[{"given":"Peiqiang","family":"Su","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinguang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilesh","family":"Patil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher S.","family":"Mow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin C.","family":"Mason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongsheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,5,31]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-133-8-200010170-00016"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/10623320600904211"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00402-007-0367-y"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042480"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-007-0354-y"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/2005"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)07226-7"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.81B4.9393"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.67B1.3155745"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.3928\/0090-4481-19991201-09"},{"key":"e_1_2_6_12_2","first-page":"460","article-title":"Easy calculations of lod scores and genetic risks on small computers","volume":"36","author":"Lathrop GM","year":"1984","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(05)70009-7"},{"key":"e_1_2_6_14_2","first-page":"7","volume-title":"Atlas of practical anatomy","author":"Gao SL","year":"2004"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.23491","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.23491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T15:03:26Z","timestamp":1697036606000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.23491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,31]]},"references-count":13,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1002\/art.23491"],"URL":"https:\/\/doi.org\/10.1002\/art.23491","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,31]]}}}