{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:04:59Z","timestamp":1792184699990,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T00:00:00Z","timestamp":1118102400000},"content-version":"vor","delay-in-days":4526,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1993,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen. Short\u2010pulse labeling of dermal fibroblasts with [<jats:sup>3<\/jats:sup>H]proline from affected individuals in 19 families indicates that most have alterations in the expected 2:1 synthetic ratio of pro\u03b11(I): pro\u03b12(I), with most having decreased production of pro\u03b11(I). Ratios of COL1A1:COL1A2 mRNA from these individuals, using slot\u2010blot hybridization, indicate that they fall into different groups, but that most have decreased COL1A1 mRNA levels, compared with controls. These data suggest that most of our OI I families have COL1A1 mutations. Copy number and size of the COL1A1 gene by restriction endonuclease analysis of genomic DNA from affected individuals are normal in the families examined. We have identified one 3 generation family in which all affected members have one normal COL1A1 allele and another with a 5 base\u2010pair deletion near the 3\u2032 end of the gene. The deletion creates a shift in the translational reading\u2010frame and predicts the synthesis of an elongated pro\u03b11(I) chain. In a second family, a father and a son have a single exon deletion that results from a splicing mutation. Chemical cleavage analysis of amplified cDNA from affected individuals in different regions of the COL1A1 gene, including the promoter, suggests that several individuals have point mutations within the coding region of the gene, while one individual may have a small deletion within the \u03b11(I) carboxyl\u2010terminal propeptide region. Our data provide evidence for significant molecular heterogeneity within the OI type I phenotype and indicate that a variety of mutations can result in decreased synthesis of type I collagen.<\/jats:p>","DOI":"10.1002\/ajmg.1320450214","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T16:39:13Z","timestamp":1118507953000},"page":"223-227","source":"Crossref","is-referenced-by-count":34,"title":["Molecular heterogeneity in osteogenesis imperfecta type I"],"prefix":"10.1002","volume":"45","author":[{"given":"Marcia C.","family":"Willing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Pruchno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Byers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.12.3838"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.9.2870"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"7021","DOI":"10.1016\/S0021-9258(18)48196-3","article-title":"Lethal perinatal osteogenesis imperfecta due to substitution of arginine for glycine at residue 391 of the \u03b1 1(I) chain of type I collagen","volume":"262","author":"Bateman JF","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110815"},{"key":"e_1_2_1_6_1","first-page":"2805","volume-title":"The Metabolic Basis of Inherited Diseases","author":"Byers PH","year":"1989"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.12.4397"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.2.802"},{"key":"e_1_2_1_9_1","first-page":"209","volume-title":"Biotechnology and Human Genetic Predisposition to Disease","author":"Dahl H\u2010HM","year":"1990"},{"key":"e_1_2_1_10_1","doi-asserted-by":"crossref","first-page":"14358","DOI":"10.1016\/S0021-9258(17)43873-7","article-title":"The mRNAs for the pro\u03b1 1(I) and pro\u03b1 2(I) chain of type I procollagen are translated at the same rate in normal human fibroblasts and in fibroblasts from two variants of osteogenesis imperfecta with altered steady state ratios of the two mRNAs","volume":"258","author":"de Wet WJ","year":"1983","journal-title":"J Biol Chem"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90432-7"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0934-8832(89)80024-1"},{"key":"e_1_2_1_13_1","unstructured":"PruchnoCJ WillingMC StarmanBJ BienkowskiRS AylsworthA ByersPH:Single nucleotide substitution in the 3\u2032 splice\u2010acceptor site of intron 16 of the COL1A1 gene causes exon skipping decreased steady\u2010state mRNA from the mutant allele and results in osteogenesis imperfecta type I. Manuscript in preparation."},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"e_1_2_1_15_1","doi-asserted-by":"crossref","first-page":"11129","DOI":"10.1016\/S0021-9258(18)90631-9","article-title":"Cysteine in the triple\u2010helical domain of one allelic product of the \u03b1 1(I) gene of type I collagen produces a lethal form of osteogenesis imperfecta","volume":"259","author":"Steinmann B","year":"1984","journal-title":"J Bio Chem"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197705262962104"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)91609-0"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.5.411"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112735"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00278784"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.1016\/S0021-9258(18)68560-6","article-title":"Arginine for glycine substitution in the triple\u2010helical domain of the products of one \u03b1 2(I) collagen allele (COL1A2) produces the osteogenesis imperfecta type IV phenotype","volume":"263","author":"Wenstrup RJ","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_1_22_1","first-page":"975","article-title":"Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta","volume":"46","author":"Wenstrup RJ","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.16.4968"},{"key":"e_1_2_1_24_1","doi-asserted-by":"crossref","first-page":"8398","DOI":"10.1016\/S0021-9258(18)68491-1","article-title":"Heterozygosity for a large deletion in the \u03b1 2(I) collagen gene has a dramatic effect on type I collagen secretion and produces perinatal lethal osteogenesis imperfecta","volume":"263","author":"Willing MC","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114424"}],"container-title":["American Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.1320450214","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.1320450214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T19:45:50Z","timestamp":1698176750000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.1320450214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,1,15]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1993,1,15]]}},"alternative-id":["10.1002\/ajmg.1320450214"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.1320450214","archive":["Portico"],"relation":{},"ISSN":["0148-7299","1096-8628"],"issn-type":[{"value":"0148-7299","type":"print"},{"value":"1096-8628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,1,15]]}}}