Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene.
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.
Lichter-Konecki
U
U
Universitaets-Kinderklinic, Heidelberg, FRG.
Konecki
D S
DS
DiLella
A G
AG
Brayton
K
K
Marvit
J
J
Hahn
T M
TM
Trefz
F K
FK
Woo
S L
SL
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
D010651:Phenylalanine Hydroxylase; D004262:DNA Restriction Enzymes