Titre
A splice mutation in the GTP cyclohydrolase I gene causes dopa-responsive dystonia by exon skipping
Type
étude de cas
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Journal of Inherited Metabolic Disease
Auteur(s)
Skrygan, M.
Auteure/Auteur
Bartholome, B.
Auteure/Auteur
Bonafe, L.
Auteure/Auteur
Blau, N.
Auteure/Auteur
Bartholome, K.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0141-8955
Statut éditorial
Publié
Date de publication
2001-06
Volume
24
Numéro
3
Première page
345
Dernière page/numéro d’article
51
Peer-reviewed
Oui
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.
Sujets
PID Serval
serval:BIB_7213C4F0B6AC
PMID
Date de création
2008-01-21T11:50:48.844Z
Date de création dans IRIS
2025-05-21T04:34:28Z