Identification of a novel splice-site mutation in the CYP1A2 gene.

Détails

ID Serval
serval:BIB_45CA4F4DA728
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
Titre
Identification of a novel splice-site mutation in the CYP1A2 gene.
Périodique
British journal of clinical pharmacology
Auteur(s)
Allorge D., Chevalier D., Lo-Guidice J.M., Cauffiez C., Suard F., Baumann P., Eap C.B., Broly F.
ISSN
0306-5251
Statut éditorial
Publié
Date de publication
2003
Peer-reviewed
Oui
Volume
56
Numéro
3
Pages
341-4
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
AIMS: To identify the molecular basis for a low CYP1A2 metabolic status, as determined by a caffeine phenotyping test, in a 71-year-old, nonsmoking, Caucasian woman who presented with very high clozapine concentrations despite being administered a standard dose of the drug. METHODS: The nucleotide sequence of the 7 exons, exon-intron boundaries and 5'-flanking region of the CYP1A2 gene was analysed by direct sequencing. RESULTS: Only one heterozygous point mutation was identified in the donor splice site of intron 6 (3534G > A) of CYP1A2. This mutation could cause abnormal RNA splicing and therefore lead to a truncated nonfunctional enzyme. No other carrier of this mutation was identified in a population of 100 unrelated healthy Caucasians. CONCLUSIONS: This is the first report of a splice-site mutation affecting the CYP1A2 gene. This polymorphism is a likely explanation for the low CYP1A2 activity associated with high clozapine concentrations in this patient.
Mots-clé
Aged, Base Sequence, Caffeine, Clozapine, Cytochrome P-450 CYP1A2, Exons, Female, Humans, Introns, Mutation, Phenotype, Polymerase Chain Reaction, Polymorphism, Genetic, Polymorphism, Single-Stranded Conformational, Psychotic Disorders, RNA Splice Sites
Pubmed
Web of science
Création de la notice
10/03/2008 11:53
Dernière modification de la notice
03/03/2018 16:46
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