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Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene.
Universitaets-Kinderklinic, Heidelberg, FRG.
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.
PMID: 2840952 [PubMed - indexed for MEDLINE]
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Cited by 17 PubMed Central articles
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Molecular analysis of contiguous exons of the phenylalanine hydroxylase gene: identification of a new PKU mutation.
Dianzani I, Camaschella C, Saglio G, Ferrero GB, Ramus S, Ponzone A, Cotton RG.
J Med Genet. 1993 Mar; 30(3):228-31.
[J Med Genet. 1993]
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Novel PKU mutation on haplotype 2 in French-Canadians.
John SW, Rozen R, Laframboise R, Laberge C, Scriver CR.
Am J Hum Genet. 1989 Dec; 45(6):905-9.
[Am J Hum Genet. 1989]
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ReviewMolecular genetics of phenylketonuria and its implications.
Levy HL.
Am J Hum Genet. 1989 Nov; 45(5):667-70.
[Am J Hum Genet. 1989]
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