ABSTRACT
We describe two previously unrecognized splice site mutations of GCH1 in Dopa responsive dystonia (DRD). Both mutations affect consensus splice acceptor (AG) sites. The first mutation is an A→G transition at position -2 of intron 1 of GCH1. This mutation results in skipping of exon 2. Fusion of exons 1 and 3 causes a frame shift that generates a premature stop codon. The second mutation is an A→G transition at position -2 of intron 2. The mutation generates a new splice acceptor site AG one base pair upstream of the wild-type splice site. This, together with a pyrimidine stretch upstream of the new splice site, renders this site functional and generates a transcript with the insertion of one base, i.e. the G of the wild-type splice site. This in turn causes a frame shift including the introduction of a premature stop codon. The two different mutations generate truncated GTP cyclohydrolase polypeptides.
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Received June 6, 1997; Revised and Accepted July 2, 1997
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Weber, Y., Steinberger, D., Deuschl, G. et al. Two previously unrecognized splicing mutations of GCH1 in Dopa-responsive dystonia: exon skipping and one base insertion. Neurogenetics 1, 125–127 (1997). https://doi.org/10.1007/s100480050018
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DOI: https://doi.org/10.1007/s100480050018