{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:24:26Z","timestamp":1791926666892,"version":"4.3.4"},"reference-count":68,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T00:00:00Z","timestamp":1117756800000},"content-version":"vor","delay-in-days":5754,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1989,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent data from several laboratories have established that most variants of osteogenesis imperfecta (OI) are caused by mutations in the 2 structural genes for type I procollagen. There are 2 general reasons for the large number of mutations in type I procollagen in OI. One reason is that most of the structure of the procollagen monomer is essential for normal biological function of the protein. The second reason is that most of the mutations cause synthesis of structurally altered pro\u03b1 chains of type I procollagen. The deleterious effects of the structurally altered pro\u03b1 chains are then amplified by at least 3 mechanisms. One mechanism is a phenomenon referred to as \u201cprocollagen suicide\u201d whereby altered pro\u03b1 chains cause degradation of normal pro\u03b1 chains synthesized by the same cell. Another mechanism involves the fact that many of the structurally altered pro\u03b1 chains prevent normal processing of the N\u2010propeptides of procollagen and persistence of the N\u2010propeptide interferes with normal fibril assembly. A third mechanism is a recently discovered phenomenon in which a substitution of a bulkier amino acid for glycine can cause a kink in the triple helix of the molecule. The kinked collagen, in turn, causes formation of abnormally branched fibrils. Because the deleterious effects of abnormal pro\u03b1 chains are amplified by these 3 mechanisms, most of the mutations are dominant and many are dominant lethal.<\/jats:p><jats:p>The conclusion that most variants of OI are caused by mutations in the structural genes for type I procollagen has broad implications for other diseases that affect connective tissue, diseases such as chondrodystrophies, osteoarthritis, and osteoporosis.<\/jats:p>","DOI":"10.1002\/ajmg.1320340112","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T13:27:54Z","timestamp":1118496474000},"page":"60-67","source":"Crossref","is-referenced-by-count":76,"title":["Type I procollagen: The gene\u2010protein system that harbors most of the mutations causing osteogenesis imperfecta and probably more common heritable disorders of connective tissue"],"prefix":"10.1002","volume":"34","author":[{"given":"Darwin J.","family":"Prockop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos D.","family":"Constantinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Dombrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl E.","family":"Kadler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Kuivaniemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Tromp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00291667"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1016\/S0021-9258(19)81713-1","article-title":"A single base mutation that converts glycine 907 of the\u03b12(I) chain of type I procollagen to aspartate in a lethal variant of osteogenesis imperfecta. The single amino acid substitution near the carboxyterminus destablizes the whole triple helix","volume":"264","author":"Baldwin CT","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_1_4_1","first-page":"508","article-title":"Exon 33 of pro\u03b12(I) collagen is deleted in mRNAs from a patient with osteogenesis imperfecta. 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