title: An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution.
abstract: The cytochrome P450 CYP2D6 is a polymorphic enzyme, for which 5%-10% of Caucasians (poor metabolizers) lack activity. The majority of mutations giving rise to the deficiency have now been identified but some individuals show anomalous phenotype-genotype relationships when screened for the common mutant alleles. We have sequenced all nine exons and intron-exon boundaries in a subject who was phenotypically a poor metabolizer but genotypically heterozygous when screened for the common alleles. A single base-pair deletion (T1795) was detected in exon 3 and a base substitution (G2064A) resulting in an amino acid substitution (G212E) in exon 4. The deletion results in premature termination of translation and a truncated protein. In a group of 50 white Americans, the allele frequency for the new mutant allele was 0.01. The new allele explains some cases of anomalous genotype/phenotype relationships for CYP2D6.
authors.affiliation: Department of Pharmacological Sciences, University of Newcastle upon Tyne, Medical School, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Daly
authors.forename: J B
authors.initials: JB
authors.lastname: Leathart
authors.forename: S J
authors.initials: SJ
authors.lastname: London
authors.forename: J R
authors.initials: JR
authors.lastname: Idle
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D003647:Debrisoquin / Q000378:metabolism*; D005796:Genes; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin