B. Goebelschreiner et R. Schreiner, IDENTIFICATION OF A NEW MISSENSE MUTATION IN JAPANESE PHENYLKETONURICPATIENTS, Journal of inherited metabolic disease, 16(6), 1993, pp. 950-956
A new missense mutation in the phenylalanine hydroxylase (PAH) gene wa
s 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 sequen
ce analysis after polymerase chain reaction (PCR) amplification and al
lele-specific oligonucleotide (ASO) hybridization. This point mutation
, an A to G transition at the first base of codon 276 in exon 7, resul
ted in an amino acid substitution. Methionine was replaced by valine a
nd the mutation was found to be associated with restriction fragment l
ength polymorphism (RFLP) haplotype 4 in the investigated patients. Th
e mutation was not found in 24 unrelated Caucasian patients from diffe
rent countries. These findings may indicate a founder effect in the tr
ansmission of the mutation.