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

Journal Article · Sat Jun 15 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.12.5423· OSTI ID:5932147

Spotila, L D; Constantinou, C D; Sereda, L; Ganguly, A; Prockop, D J ^[1]; Riggs, B L ^[2]

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1. Jefferson Medical College, Philadelphia, PA (United States)
2. Mayo Clinic, Rochester, MN (United States)

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, the authors show that a 52-year-old post menopausal woman with severe osteopenia and a compression fracture of a thoracic vertebra had a mutation in the gene for the {alpha}2(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 {alpha}2(I) chain. Further analysis demonstrated a single-base mutation that caused a serine-for-glycine substitution at position 661 of the {alpha}2(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.

• OSTI ID: 5932147
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:12; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550602* -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMALS
BIOMEDICAL RADIOGRAPHY
BODY
CARBOXYLIC ACIDS
COLLAGEN
DIAGNOSTIC TECHNIQUES
DISEASES
DNA SEQUENCING
ELECTROPHORESIS
ETIOLOGY
FEMALES
GENE MUTATIONS
GLYCINE
MAMMALS
MAN
MEDICINE
MUTATIONS
NUCLEAR MEDICINE
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OSTEOPOROSIS
PRIMATES
PROTEINS
RADIOLOGY
SCLEROPROTEINS
SKELETAL DISEASES
SKELETON
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRAE
VERTEBRATES
WOMEN