Identification of a new missense mutation in Japanese phenylketonuric patients.

A new missense mutation in the phenylalanine hydroxylase (PAH) gene was identified in 20/30 members of the families of 10 unrelated Japanese phenylketonuria (PKU) patients from Kyushu island. The point mutation was present in 20 of 40 mutant alleles. This was proved by DNA sequence analysis after polymerase chain reaction (PCR) amplification and allele-specific oligonucleotide (ASO) hybridization. This point mutation, an A to G transition at the first base of codon 276 in exon 7, resulted in an amino acid substitution. Methionine was replaced by valine and the mutation was found to be associated with restriction fragment length polymorphism (RFLP) haplotype 4 in the investigated patients. The mutation was not found in 24 unrelated Caucasian patients from different countries. These findings may indicate a founder effect in the transmission of the mutation.