{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:51:55Z","timestamp":1788871915533,"version":"build-2803163510"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1994,6,1]],"date-time":"1994-06-01T00:00:00Z","timestamp":770428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR38188"],"award-info":[{"award-number":["AR38188"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["Prockop"],"award-info":[{"award-number":["Prockop"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shriners Hospitals for Crippled Children","award":["(15958 Whyte)"],"award-info":[{"award-number":["(15958 Whyte)"]}]},{"name":"March of Dimes\/Birth Defects Foundation"},{"DOI":"10.13039\/100011517","name":"Lucille P. Markey Charitable Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011517","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1994,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutations in one of the two genes encoding type I procollagen (COL1A1 and COL1A2) are frequently the cause of osteogenesis imperfecta (OI), a disorder characterized by brittle bones. Here we tested whether patients with low bone density also have mutations in these genes. The 26 patients studied had no apparent metabolic bone disease, but most had a positive family history of osteopenia or osteoporosis. Although a diagnosis of OI was considered by the clinician in some cases, the clinical criteria for OI were not satisfied. Our strategy for mutation analysis consisted of PCR amplification of cDNA made to fibroblast mRNA using primers specific for the coding regions of COL1A1 and COL1A2. The PCR products were then sequenced directly with primers located within each PCR product. We found that 3 of 26 patients had mutations that altered the encoded amino acid. One mutation, at position \u03b12(I)-661 has been reported (Spotila et al. 1991 Proc Natl Acad Sci USA PNAS 88: 5423). The other 2 patients, who were not related to each other, had a mutation that altered the proline codon at \u03b11(I)-27 to alanine. This mutation was not found in 81 normal individuals or in 37 additional osteopenic individuals. However, its effect on the biologic function of type I collagen, as well as its role in osteopenia, is uncertain. In addition to the two mutations, we found a polymorphism in codon \u03b12(I)-459. Although this polymorphism involved an amino acid substitution, it was present with equal frequency in the patient and the normal population. By analyzing this and previously reported neutral sequence variants in the COL1A2 gene, we determined that all patients expressed both alleles of the COL1A2 gene. The 12 patients who were heterozygous for a COL1A1 neutral sequence variant also expressed both alleles. Here we present all PCR primer and sequencing primer information. The results suggest that surveying a larger group of similarly selected individuals may reveal additional mutations in the COL1A1 or COL1A2 genes.<\/jats:p>","DOI":"10.1002\/jbmr.5650090618","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T11:32:53Z","timestamp":1265196773000},"page":"923-932","source":"Crossref","is-referenced-by-count":71,"title":["Mutation analysis of coding sequences for type I procollagen in individuals with low bone density"],"prefix":"10.1093","volume":"9","author":[{"given":"Loretta D.","family":"Spotila","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Colige","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Liege, Li\u00e8ge, Belgium"},{"name":"Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Sereda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos D.","family":"Constantinou-Deltas","sequence":"additional","affiliation":[{"name":"Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus"},{"name":"Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Whyte","sequence":"additional","affiliation":[{"name":"Shriners Hospital for Crippled Children, St. Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence B.","family":"Riggs","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Shaker","sequence":"additional","affiliation":[{"name":"St. Luke's Medical Center, Milwaukee, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Spector","sequence":"additional","affiliation":[{"name":"Medical College of St. Bartholomew's Hospital, London, England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hume","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Olsen","sequence":"additional","affiliation":[{"name":"Vanderbilt University, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice","family":"Attie","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, Pennsylvania. Deceased"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Tenenhouse","sequence":"additional","affiliation":[{"name":"Montreal General Hospital, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Shane","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians and Surgeons, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Briney","sequence":"additional","affiliation":[{"name":"Denver Arthritis Clinic, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darwin J.","family":"Prockop","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Jefferson Medical College, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[1994,6,1]]},"reference":[{"key":"2024013113134464500_bib1","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1096\/fasebj.5.7.2010058","article-title":"Mutations in collagen genes: Causes of rare and some common diseases in humans","volume":"5","author":"Kuivaniemi","year":"1991","journal-title":"FASEB J"},{"key":"2024013113134464500_bib2","doi-asserted-by":"crossref","first-page":"4333","DOI":"10.1136\/jmg.28.7.433","article-title":"Osteogenesis imperfecta: Translation of mutation to phenotype","volume":"28","author":"Byers","year":"1991","journal-title":"J Med Genet"},{"issue":"4","key":"2024013113134464500_bib3","first-page":"434","article-title":"Osteogenesis imperfecta type I commonly due to COL1A1 null allele","volume":"49","author":"Willing","year":"1991","journal-title":"Am J Hum Genet Suppl"},{"key":"2024013113134464500_bib4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/ajmg.1320340114","article-title":"Inherited disorders of collagen gene structure and expression","volume":"34","author":"Byers","year":"1989","journal-title":"Am J Med Genet"},{"key":"2024013113134464500_bib5","first-page":"1680","volume-title":"Harrison's Principles of Internal Medicine","author":"Prockop","year":"1987","edition":"11th ed."},{"key":"2024013113134464500_bib6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/ajmg.1320340112","article-title":"Type I procollagen: The gene-protein system that harbors most of the mutations causing osteogenesis imperfecta and probably more common heritable disorders of connective tissue","volume":"34","author":"Prockop","year":"1989","journal-title":"Am J Med Genet"},{"key":"2024013113134464500_bib7","doi-asserted-by":"crossref","first-page":"5423","DOI":"10.1073\/pnas.88.12.5423","article-title":"Mutation in the gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: Evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta","volume":"88","author":"Spotila","year":"1991","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013113134464500_bib8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0934-8832(11)80049-1","article-title":"Three new COL1A2 polymorphisms","volume":"12","author":"Strobel","year":"1992","journal-title":"Matrix"},{"key":"2024013113134464500_bib9","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1093\/nar\/18.18.5577","article-title":"PvuII polymorphism at the COL1A2 locus","volume":"18","author":"Constantinou","year":"1990","journal-title":"Nucleic Acids Res"},{"key":"2024013113134464500_bib10","first-page":"194","volume-title":"Molecular Cloning. 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