A novel CYP2D6 allele with an abolished splice recognition site associated with the poor metabolizer phenotype.
A novel loss-of function allele of the CYP2D6 gene was characterized in a PM individual using exon-by-exon PCR-SSCP analysis. This allele, we termed CYP2D6(F), harbours four mutations including a new mutation (D6-F) which abolishes the splice acceptor site of the 1st intron and results in a premature stop codon. DNA samples from a large population of healthy unrelated volunteers were tested for D6-F using a PCR-assay we developed for the specific identification of the mutation in genomic DNA. The prevalence of D6-F was very low. However, its identification combined with that of the previously reported gene inactivating mutations would further increase the phenotype prediction rate by genotyping.
Marez
D
D
Laboratoire de Biochimie et Biologie Moléculaire de l'Hôpital Calmette, Centre Hospitalier Régional et Universitaire de Lille, France.
Sabbagh
N
N
Legrand
M
M
Lo-Guidice
J M
JM
Boone
P
P
Broly
F
F
D000483:Alleles; D001483:Base Sequence; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers; D005091:Exons; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D015183:Restriction Mapping
D017931:DNA Primers; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6