title: Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene.
abstract: A novel restriction fragment length polymorphism in the phenylalanine hydroxylase (PAH) locus generated by the restriction endonuclease MspI was observed in a German phenylketonuria (PKU) patient. Molecular cloning and DNA sequence analyses revealed that the MspI polymorphism was created by a T to C transition in exon 9 of the human PAH gene, which also resulted in the conversion of a leucine codon to a proline codon. The effect of the amino acid substitution was investigated by creating a corresponding mutation in a full-length human PAH cDNA by site-directed mutagenesis followed by expression analysis in cultured mammalian cells. Results demonstrate that the mutation in the gene causes the synthesis of an unstable protein in the cell corresponding to a CRM- phenotype. Together with the other mutations recently reported in the PAH gene, the data support previous biochemical and clinical observations that PKU is a heterogeneous disorder at the gene level.
authors.affiliation: Universitaets-Kinderklinic, Heidelberg, FRG.
authors.forename: U
authors.initials: U
authors.lastname: Lichter-Konecki
authors.forename: D S
authors.initials: DS
authors.lastname: Konecki
authors.forename: A G
authors.initials: AG
authors.lastname: DiLella
authors.forename: K
authors.initials: K
authors.lastname: Brayton
authors.forename: J
authors.initials: J
authors.lastname: Marvit
authors.forename: T M
authors.initials: TM
authors.lastname: Hahn
authors.forename: F K
authors.initials: FK
authors.lastname: Trefz
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
mesh_terms: D001483:Base Sequence; D004262:DNA Restriction Enzymes; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010651:Phenylalanine Hydroxylase / Q000172:deficiency / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics
chemical_list: D010651:Phenylalanine Hydroxylase; D004262:DNA Restriction Enzymes