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Neurosci Lett. 1999 Feb 5;260(3):181-4.

A novel missense mutant inactivates GTP cyclohydrolase I in dopa-responsive dystonia.

Author information

1
Department of Medical Genetics, Nara Medical University, Kashihara, Japan.

Abstract

Dopa-responsive dystonia (DRD) due to mutant GTP cyclohydrolase I (GCH) shows the considerable heterogeneity of clinical phenotypic expression. To explain the clinical diversity, we studied a Japanese family with a novel mutant GCH (GCH-G90V), where an affected heterozygote had a higher mutant/normal mRNA ratio than an unaffected heterozygote. Coexpression experiments using the mutant with wild-type GCH showed that GCH-G90V inactivated the normal enzyme in a dose-dependent manner, suggesting that the dominant negative effect of a mutant GCH on the normal enzyme might be one of the molecular mechanisms for the clinical heterogeneity of DRD.

PMID:
10076897
DOI:
10.1016/s0304-3940(98)00984-7
[Indexed for MEDLINE]

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