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 proline codon. The effect of the amino acid substitution was investigated by creating a corresponding mutation in a full-length human PAD 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/sup -/ 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.
- Research Organization:
- Universitaets-Kinderklinic, Heidelberg (West Germany)
- OSTI ID:
- 7143150
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:8; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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550401* -- Genetics-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DNA
DNA SEQUENCING
ENZYME ACTIVITY
ENZYMES
EVEN-ODD NUCLEI
GENE MUTATIONS
GENES
GENETIC MAPPING
HYDROXYLASES
ISOTOPES
LIGHT NUCLEI
MAPPING
MUTAGENESIS
MUTATIONS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PATIENTS
PHENYLALANINE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RECESSIVE MUTATIONS
RECOMBINANT DNA
STRUCTURAL CHEMICAL ANALYSIS
SULFUR 35
SULFUR ISOTOPES