Phenylalanine hydroxylase gene: silent mutation uncovers evolutionary origin of different alleles

Abstract
Analyzing a panel of 94 phenylketonuria (PKU) alleles for mutations within the phenylalanine hydroxylase (PAH) gene, we identified a G to A transition in exon 7 corresponding to nucleotide 957 in the cDNA sequence. This nucleotide substitution generates a new Alu I site (...GTGGCT... .fwdarw. ...GTAGCT...), but does not change the encoded amino acid (GTG245 .fwdarw. GTA245 = VAL). In our panel of patients the Alu I polymorphism is exclusively associated with haplotypes 4 (mutant or normal alleles) and 3, 16, 17, 28 (normal alleles).