Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy).
Publication/Presentation Date
8-1-1991
Abstract
Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at alpha 1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein.
Volume
88
Issue
15
First Page
6624
Last Page
6627
ISSN
0027-8424
Published In/Presented At
Ahmad, N. N., Ala-Kokko, L., Knowlton, R. G., Jimenez, S. A., Weaver, E. J., Maguire, J. I., Tasman, W., & Prockop, D. J. (1991). Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy). Proceedings of the National Academy of Sciences of the United States of America, 88(15), 6624–6627. https://doi.org/10.1073/pnas.88.15.6624
Disciplines
Medicine and Health Sciences
PubMedID
1677770
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article