A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping

Details

Serval ID
serval:BIB_7213C4F0B6AC
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping
Journal
Journal of Inherited Metabolic Disease
Author(s)
Skrygan  M., Bartholome  B., Bonafe  L., Blau  N., Bartholome  K.
ISSN
0141-8955
Publication state
Published
Issued date
06/2001
Peer-reviewed
Oui
Volume
24
Number
3
Pages
345-51
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun
Abstract
Four different mutations in the GTP cyclohydrolase I gene were found (P199L, M211V, IVS5+1G>A, G203R) in 6 out of 33 families with dopa-responsive dystonia. A splice mutation (IVS5+1G>A) located at the border of exon 5 to intron 5 was found in one of these families. Three members of the family carry the IVS5+1G>A mutation on one allele, inherited from the father to the daughter and son. Examination of the mRNA showed an exon 5 skipping that results in a reduction of enzyme activity in cultured fibroblasts to 4-17% compared to controls. The father and daughter never had clinical symptoms of dopa-responsive dystonia. The son was symptomatic at the age of 3 years and was treated successfully with L-dopa/carbidopa. After 20 years this therapy was terminated and for the next 6 years he was free of symptoms. With increased motoric activity, symptoms reappeared and the therapy was reintroduced.
Keywords
Alleles Amino Acid Sequence Base Sequence Benserazide/therapeutic use Biopterin/metabolism Cells, Cultured Child, Preschool Dihydroxyphenylalanine/*therapeutic use Dopa Decarboxylase/antagonists & inhibitors Drug Combinations Dystonia/drug therapy/*genetics Enzyme Inhibitors/pharmacology Exons Female Fibroblasts/metabolism GTP Cyclohydrolase/chemistry/*genetics Humans Introns Levodopa/therapeutic use Male *Mutation Neopterin/biosynthesis *RNA Splicing RNA, Messenger/analysis
Pubmed
Web of science
Create date
21/01/2008 12:50
Last modification date
20/08/2019 14:30
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