Translational read‐through of a nonsense mutation in ATP7A impacts treatment outcome in Menkes disease
- 1 January 2009
- journal article
- case report
- Published by Wiley in Annals of Neurology
- Vol. 65 (1), 108-113
- https://doi.org/10.1002/ana.21576
Abstract
Protein translation ends when a stop codon in a gene's messenger RNA transcript enters the ribosomal A site. Mutations that create premature stop codons (nonsense mutations) typically cause premature translation termination. An alternative outcome, read‐through translation (or nonsense suppression), is well known in prokaryotic, viral, and yeast genes but has not been clearly documented in humans except in the context of pharmacological manipulations. Here, we identify and characterize native read‐through of a nonsense mutation (R201X) in the human copper transport gene, ATP7A. Western blotting, in vitro expression analyses, immunohistochemistry, and yeast complementation assays using cultured fibroblasts from a classic Menkes disease patient all indicated small amounts of native ATP7AR201X read‐through and were associated with a dramatic clinical response to early copper treatment. Ann Neurol 2009;65:108–113Keywords
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