{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T14:04:17Z","timestamp":1767276257187,"version":"build-2065373602"},"reference-count":30,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1991,11]]},"abstract":"<jats:p>We have examined the type I collagen in a patient with type III\/IV osteogenesis imperfecta. Two forms of alpha 1(I) chain were produced, one normal and the other containing a cysteine residue within the triple helical domain of the molecule. Cysteine is not normally present in this domain of type I collagen. Peptide mapping experiments localised the mutation to peptide alpha 1(I)CB3 which spans residues 403 to 551 of the triple helix. Subsequent PCR amplification of cDNA covering this region followed by sequencing showed a G to T single base change in the GGC codon for glycine 415 generating TGC, the codon for cysteine. The effect of the mutation on the protein is to delay secretion from the cell, reduce the thermal stability of the molecule by 2 degrees C, and cause excessive post-translational modification of all chains in molecules containing one or more mutant alpha 1(I) chains. The clinical phenotype observed in this patient and the position of the mutation conform to the recent prediction of Starman et al that Gly----Cys mutations in the alpha 1(I) chain have a gradient of severity decreasing from the C-terminus to the N-terminus.<\/jats:p>","DOI":"10.1136\/jmg.28.11.757","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:11:11Z","timestamp":1226329871000},"page":"757-764","source":"Crossref","is-referenced-by-count":18,"title":["Substitution of cysteine for glycine at residue 415 of one allele of the alpha 1(I) chain of type I procollagen in type III\/IV osteogenesis imperfecta."],"prefix":"10.1136","volume":"28","author":[{"given":"A C","family":"Nicholls","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Oliver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D V","family":"Renouf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Keston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F M","family":"Pope","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1991,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/S0021-9258(20)71150-6","article-title":"Multiexon deletion in an osteogenesis imperfecta variant with increased type III collagen mRNA","volume":"260","author":"Chu, M.L.; Gargiulo, V.; Williams, C.J.; Ramirez, F.","year":"1985","unstructured":"Chu ML, Gargiulo V, Williams CJ, Ramirez F. Multiexon deletion in an osteogenesis imperfecta variant with increased type III collagen mRNA. J Biol Chem 1985;260:691-4.","journal-title":"J Biol Chem"},{"key":"ref_2","first-page":"2870","article-title":"Intron mediated recombination may cause a deletion in an al type I collagen chain in a lethal form","volume-title":"of osteogenesis imperfecta. Proc Natl Acad Sci","volume":"82","author":"Barsh, G.S.; Roush, C.L.; Bonadio, J.; Byers, P.H.; Gelinas, R.E.","year":"1985","unstructured":"Barsh GS, Roush CL, Bonadio J, Byers PH, Gelinas RE. Intron mediated recombination may cause a deletion in an al type I collagen chain in a lethal form of osteogenesis imperfecta. Proc Natl Acad Sci USA 1985;82:2870-4."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7855","DOI":"10.1016\/S0021-9258(18)68576-X","article-title":"A novel mutation causes a perinatal lethal form of osteogenesis imperfecta-an insertion in one al(I) allele (COLlAI)","volume":"263","author":"Byers, P.H.; Starman, B.J.; Cohn, D.H.; Horwitz, A.L.","year":"1988","unstructured":"Byers PH, Starman BJ, Cohn DH, Horwitz AL. A novel mutation causes a perinatal lethal form of osteogenesis imperfecta-an insertion in one al(I) allele (COLlAI). J Biol Chem 1988;263:7855-61.","journal-title":"J Biol Chem"},{"key":"ref_4","first-page":"5254","article-title":"Single base mutation in the proa2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but","volume-title":"inframe proa2(I) chain. Proc Natl Acad Sci","volume":"85","author":"Tromp, G.; Prockop, D.J.","year":"1988","unstructured":"Tromp G, Prockop DJ. Single base mutation in the proa2(I) collagen gene that causes efficient splicing of RNA from exon 27 to exon 29 and synthesis of a shortened but inframe proa2(I) chain. Proc Natl Acad Sci USA 1988;85:5254-8."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11407","DOI":"10.1016\/S0021-9258(18)37971-7","article-title":"A 19-base pair deletion in the pro a2(I) gene of type I procollagen that causes in-frame RNA splicing from exon 10 to exon 12 in a proband with atypical osteogenesis imperfecta and his asymptomatic mother","volume":"263","author":"Kuivaniemi, H.; Sabol, C.; Tromp, G.; Sippola-Thiele, M.; Prockop, D.J.","year":"1988","unstructured":"Kuivaniemi H, Sabol C, Tromp G, Sippola-Thiele M, Prockop DJ. A 19-base pair deletion in the pro a2(I) gene of type I procollagen that causes in-frame RNA splicing from exon 10 to exon 12 in a proband with atypical osteogenesis imperfecta and his asymptomatic mother. J Biol Chem 1988;263:11407-13.","journal-title":"J Biol Chem"},{"key":"ref_6","first-page":"6045","article-title":"Lethal osteogenesis imperfecta resulting from a single nucleotide change","volume-title":"one human procil(I) collagen allele. Proc Nail Acad Sci","volume":"83","author":"Cohn, D.H.; Byers, P.H.; Steinmann, B.; Gelinas, R.E.","year":"1986","unstructured":"Cohn DH, Byers PH, Steinmann B, Gelinas RE. Lethal osteogenesis imperfecta resulting from a single nucleotide change in one human procil(I) collagen allele. Proc Nail Acad Sci USA 1986;83:6045-7."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9056","DOI":"10.1016\/S0021-9258(19)84487-3","article-title":"The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the triple helical domain of pro al(I) chains","volume":"261","author":"de Vries WN; de Wet W","year":"1986","unstructured":"de Vries WN, de Wet W. The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the triple helical domain of pro al(I) chains. J Biol Chem 1986;261:9056-64.","journal-title":"J Biol Chem"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7021","DOI":"10.1016\/S0021-9258(18)48196-3","article-title":"Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the a l(I) chain of type I collagen","volume":"262","author":"Bateman, J.F.; Chan, D.; Walker, I.D.; Rogers, J.G.; Cole, W.G.","year":"1987","unstructured":"Bateman JF, Chan D, Walker ID, Rogers JG, Cole WG. Lethal perinatal osteogenesis imperfecta due to the substitution of arginine for glycine at residue 391 of the a l(I) chain of type I collagen. J Biol Chem 1987;262:7021-7.","journal-title":"J Biol Chem"},{"issue":"1","key":"ref_9","first-page":"1627","article-title":"Substitution of arginine for glycine 664 in the collagen al(I) chain in lethal perinatal osteogenesis imperfecta","volume":"263","author":"Bateman, J.F.; Lamande, S.; Dahl, H.H.M.; Chan, D.; Cole, W.G.","year":"1988","unstructured":"Bateman JF, Lamande S, Dahl HHM, Chan D, Cole WG. Substitution of arginine for glycine 664 in the collagen al(I) chain in lethal perinatal osteogenesis imperfecta. 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J Biol Chem 1989;264:19694-9.","journal-title":"J Biol Chem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1172\/JCI113920","article-title":"A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cystine for glycine 904 of the al(I) chain of type I procollagen","volume":"83","author":"Constantinou, C.D.; Nielsen, K.B.; Prockop, D.J.","year":"1989","unstructured":"Constantinou CD, Nielsen KB, Prockop DJ. A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cystine for glycine 904 of the al(I) chain of type I procollagen. J Clin Invest 1989;83:574-84.","journal-title":"J Clin Invest"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15809","DOI":"10.1016\/S0021-9258(18)71548-2","article-title":"Characterization of point mutations in the collagen COLlAl and COL1A2 genes causing lethal perinatal osteogenesis imperfecta","volume":"264","author":"Lamande, SR, Dahl; HMM, Cole; WG, Bateman; J.F.","year":"1989","unstructured":"Lamande SR, Dahl HMM, Cole WG, Bateman JF. Characterization of point mutations in the collagen COLlAl and COL1A2 genes causing lethal perinatal osteogenesis imperfecta. 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Linkage of a polymorphic marker for the type III collagen gene (COL3A1) to atypical autosomal dominant Ehlers-Danlos syndrome type IV in a large Belgian pedigree. Hum Genet 1988;78:276-81.","journal-title":"Hum Genet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/316363a0","article-title":"Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II","volume":"316","author":"Bonadio, J.; Byers, P.H.","year":"1988","unstructured":"Bonadio J, Byers PH. Subtle structural alterations in the chains of type I procollagen produce osteogenesis imperfecta type II. Nature 1988;316:363-6.","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0174-173X(81)80035-0","article-title":"Peptide mapping of collagen chains using CNBr cleavage of proteins within polyacrylamide gels","volume":"1","author":"Barsh, G.S.; Peterson, K.E.; Byers, P.H.","year":"1981","unstructured":"Barsh GS, Peterson KE, Byers PH. Peptide mapping of collagen chains using CNBr cleavage of proteins within polyacrylamide gels. Collagen Rel Res 1981;1:543-8.","journal-title":"Collagen Rel Res"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF00204180","article-title":"Ehlers Danlos syndrome type VII: a single base change that causes exon skipping in the type I collagen a2(I) chain","volume":"87","author":"Nicholls, A.C.; Oliver, J.; Renouf, D.V.; McPheat, J.; Palen, A.; Pope, F.M.","year":"1991","unstructured":"Nicholls AC, Oliver J, Renouf DV, McPheat J, Palen A, Pope FM. Ehlers Danlos syndrome type VII: a single base change that causes exon skipping in the type I collagen a2(I) chain. Hum Genet 1991;87:193-8.","journal-title":"Hum Genet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli, U.K.","year":"1970","unstructured":"Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227:680-5.","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1432-1033.1974.tb03599.x","article-title":"A film detection method for tritium labelled proteins and nucleic acids in polyacrylamide gels","volume":"46","author":"Bonner, W.M.; Laskey, R.A.","year":"1974","unstructured":"Bonner WM, Laskey RA. A film detection method for tritium labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem 1974;46:83-8.","journal-title":"Eur J Biochem"},{"key":"ref_29","first-page":"191","article-title":"Molecular cloning: a laboratory manual","author":"Maniatis, T.; Fritsch, E.F.; Sambrook, J.","year":"1982","unstructured":"Maniatis T, Fritsch EF, Sambrook J. Molecular cloning: a laboratory manual. New York: Cold Spring Harbor Laboratories, 1982: 191-3."},{"key":"ref_30","first-page":"5436","article-title":"DNA sequencing with","volume-title":"chain terminating inhibitors Proc Natl Acad Sci USA","volume":"74","author":"Sanger, F.; Nicklen, S.; Coulson, A.R.","year":"1977","unstructured":"Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain terminating inhibitors Proc Natl Acad Sci USA 1977; 74:5436-67."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.28.11.757","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T21:48:07Z","timestamp":1760737687000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.28.11.757"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,11]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[1991,11,1]]},"published-print":{"date-parts":[[1991,11]]}},"alternative-id":["10.1136\/jmg.28.11.757"],"URL":"https:\/\/doi.org\/10.1136\/jmg.28.11.757","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[1991,11]]}}}