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Br J Clin Pharmacol. 2003 Sep;56(3):341-4.

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

Author information

1
EA 2679, Faculté de Médecine/Pôle Recherche, 1 place de Verdun, F-59045 Lille cedex, France. dallorge@University-lille2.fr

Abstract

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.

PMID:
12919186
PMCID:
PMC1884342
DOI:
10.1046/j.1365-2125.2003.01858.x
[Indexed for MEDLINE]
Free PMC Article

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