title: Mutation analysis of the phenylalanine hydroxylase gene using heteroduplex analysis with synthetic DNA constructs.
abstract: Using heteroduplex analysis generated with synthetic PCR-amplifiable DNA we have screened the PKU populations of southwest England and Wales, western Scotland, and southeast and central England for mutations in exons 3, 7 and 12 of the phenylalanine hydroxylase (PAH) gene. The technique characterized three mutations in exon 12, two in exon 3 and five in exon 7. Altogether over 370 PKU chromosomes were screened. In all geographical regions exon 12 mutations (R408W, IVS12nt1g- > a and Y414C) accounted for about 40% of mutant chromosomes. Exon 3 mutations (principally I65T) were found on between 9 and 12% of mutant alleles and exon 7 mutations accounted for a further 5-7%. Heteroduplex analysis is rapid, simple and safe and three constructs covering three exons can identify between 55 and 60% of mutations in various PKU populations of the UK.
authors.affiliation: Department of Clinical Chemistry, Southmead Hospital, Bristol, UK.
authors.forename: L A
authors.initials: LA
authors.lastname: Tyfield
authors.forename: A
authors.initials: A
authors.lastname: Stephenson
authors.forename: J L
authors.initials: JL
authors.lastname: Bidwell
authors.forename: N A
authors.initials: NA
authors.lastname: Wood
authors.forename: F
authors.initials: F
authors.lastname: Cockburn
authors.forename: A
authors.initials: A
authors.lastname: Harvie
authors.forename: I
authors.initials: I
authors.lastname: Smith
mesh_terms: D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004739:England / Q000453:epidemiology; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D009692:Nucleic Acid Heteroduplexes / Q000235:genetics*; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000453:epidemiology / Q000235:genetics*; D012606:Scotland / Q000453:epidemiology; D014852:Wales / Q000453:epidemiology
chemical_list: D009692:Nucleic Acid Heteroduplexes; D004247:DNA; D010651:Phenylalanine Hydroxylase