Article: article from journal or magazin.
Case report (case report): feedback on an observation with a short commentary.
Identification of a novel splice-site mutation in the CYP1A2 gene.
British journal of clinical pharmacology
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
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.
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
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