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Science 29 January 1993:
Vol. 259. no. 5095, pp. 680 - 683
DOI: 10.1126/science.8430317
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Articles

Science, Vol 259, Issue 5095, 680-683
Copyright © 1993 by American Association for the Advancement of Science

articles

The skipping of constitutive exons in vivo induced by nonsense mutations

HC Dietz, D Valle, CA Francomano, RJ Kendzior Jr, RE Pyeritz, and GR Cutting

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Nonsense mutations create a premature signal for the termination of translation of messenger RNA. Such mutations have been observed to cause a severe reduction in the amount of mutant allele transcript or to generate a peptide truncated at the carboxyl end. Analysis of fibrillin transcript from a patient with Marfan syndrome revealed the skipping of a constitutive exon containing a nonsense mutation. Similar results were observed for two nonsense mutations in the gene encoding ornithine delta-aminotransferase from patients with gyrate atrophy. All genomic DNA sequences flanking these exons that are known to influence RNA splicing were unaltered, which suggests that nonsense mutations can alter splice site selection in vivo.


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