title: Xbal 16- plus 9-kilobase DNA restriction fragments identify a mutant allele for debrisoquin hydroxylase: report of a family study.
abstract: Previous studies have established that two Xbal polymorphic restriction fragments [11.5 and 44 kilobases (kb)] hydridizing to a full length debrisoquin hydroxylase cDNA are associated with two different mutant alleles for the debrisoquin hydroxylase gene (IID6). An independent allele, defined by Xbal 16- and 9-kb fragments, has previously been identified only in extensive metabolizers, precluding determination of whether this restriction fragment length polymorphism (RFLP) pattern identifies a functional or nonfunctional mutant allele of IID6. We phenotyped and performed RFLP studies in the family of a poor metabolizer (PM) propositus with the Xbal 16 + 9 allele. Three family members were of the PM phenotype, two of whom had the 16 + 9 allele, indicating that this RFLP pattern identified a nonfunctional IID6 allele in this family. Moreover, additional RFLP analyses indicated that the PM mother had two different IID6 mutant alleles that produce the Xbal 29-kb fragment, indistinguishable from the RFLP pattern produced by a functional IID6 allele. These data indicate that the Xbal 16 + 9 RFLP pattern can identify a mutant IID6 allele and that at least two different nonfunctional mutant alleles can produce the Xbal 29-kb fragment found in all extensive metabolizers.
authors.affiliation: Pharmaceutical Division, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
authors.forename: M V
authors.initials: MV
authors.lastname: Relling
mesh_terms: D000328:Adult; D000483:Alleles; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005796:Genes; D006580:Genetic Carrier Screening; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008970:Molecular Weight; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; C025580:endodeoxyribonuclease XBAI; D015252:Deoxyribonucleases, Type II Site-Specific