A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping
Détails
ID Serval
serval:BIB_7213C4F0B6AC
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping
Périodique
Journal of Inherited Metabolic Disease
ISSN
0141-8955
Statut éditorial
Publié
Date de publication
06/2001
Peer-reviewed
Oui
Volume
24
Numéro
3
Pages
345-51
Notes
Case Reports
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun
Résumé
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.
Mots-clé
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
Création de la notice
21/01/2008 13:50
Dernière modification de la notice
20/08/2019 15:30