Mutation in a gene for type I procollagen (COL1A2) in a woman with postmenopausal osteoporosis: evidence for phenotypic and genotypic overlap with mild osteogenesis imperfecta
| Autor: | Spotila, L. D., Constantinou-Deltas, Constantinos D., Sereda, L., Ganguly, A., Riggs, B. L., Prockop, D. J. |
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| Přispěvatelé: | Constantinou-Deltas, Constantinos D. [0000-0001-5549-9169] |
| Rok vydání: | 1991 |
| Předmět: |
Collagen helix
Osteoporosis Case Report osteogenesis imperfecta Gene mutation Support U.S. Gov't P.H.S Polymerase Chain Reaction Middle Age Osteoporosis Postmenopausal Multidisciplinary article Middle Aged Osteogenesis Imperfecta postmenopause female Phenotype priority journal Osteogenesis imperfecta Electrophoresis Polyacrylamide Gel Female Collagen Procollagen Type I collagen Research Article Adult medicine.medical_specialty Genotype Molecular Sequence Data procollagen Biology glycine substitutions posttranslational overmodifications Internal medicine direct DNA sequencing medicine Humans human Support Non-U.S. Gov't Gene collagen type 1 Base Sequence Point mutation detection of mutations medicine.disease osteoporosis human tissue Radiography Procollagen peptidase Endocrinology Mutation mutation dna sequence |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proc.Natl.Acad.Sci.U.S.A. |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Mutations in the two genes for type I collagen (COL1A1 or COL1A2) cause osteogenesis imperfecta (OI), a heritable disease characterized by moderate to extreme brittleness of bone early in life. Here we show that a 52-year-old postmenopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the α2(I) chain of type I collagen (COL1A2) similar to mutations that cause OI. cDNA was prepared from the woman's skin fibroblast RNA and assayed for the presence of a mutation by treating DNA heteroduplexes with carbodiimide. The results indicated a sequence variation in the region encoding amino acid residues 660-667 of the α2(I) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the α2(I) triple-helical domain. The substitution produced posttranslational overmodification of the collagen triple helix, as is seen with most glycine substitutions that cause OI. The patient had a history of five previous fractures, slightly blue sclerae, and slight hearing loss. Therefore, the results suggest that there may be phenotypic and genotypic overlap between mild osteogenesis imperfecta and postmenopausal osteoporosis, and that a subset of women with postmenopausal osteoporosis may have mutations in the genes for type I procollagen. 88 5423 5427 Cited By :103 |
| Databáze: | OpenAIRE |
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