Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Medline ® Abstract for Reference 94

of 'Risk factors for and possible causes of osteoarthritis'

Single base mutation in the type II procollagen gene (COL2A1) as a cause of primary osteoarthritis associated with a mild chondrodysplasia.
Ala-Kokko L, Baldwin CT, Moskowitz RW, Prockop DJ
Proc Natl Acad Sci U S A. 1990;87(17):6565.
A cosmid clone was isolated that contained an allele for the type II procollagen gene previously shown to be coinherited with primary generalized osteoarthritis in a large family. Affected members of the family had evidence of a mild chondrodysplasia, but they developed progressive osteoarthritic changes in many joints that had no epiphyseal deformities. The clone contained 52 of the 54 exons of the gene. Nucleotide sequencing of greater than 20,000 base pairs from the clone demonstrated that all the coding sequences and all the intron-exon boundaries were normal except for a single base mutation that converted the codon for arginine at position 519 of the alpha 1(II) chain to a codon for cysteine, an amino acid not found in type II collagen from humans or a variety of other species. The mutation was found in all affected members of the family but not in unaffected members or in 57 unrelated individuals.
Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-6799.