ClinVar

In a patient with classic phenylketonuria (PKU; 261600), Svensson et al. (1990) identified compound heterozygosity for a G-to-T transversion in the PAH gene, resulting in a gly272-to-ter (G272X) substitution, and a deletion of CTT leucine codon 364 (612349.0021).

In 47 Norwegian nuclear families with at least 1 child with PKU, Apold et al. (1990) found haplotype 7, which is relatively rare in other populations, in 20% of all mutant haplotypes. In 14 of the 17 mutant haplotypes 7, a deletion of the BamHI restriction site in exon 7 of the PAH gene was found. The abrogation of the site was shown to be due to a G-to-T transversion, changing glycine-272 to a stop codon in exon 7. The families with this mutation were clustered along the southeastern coast of Norway, suggesting a founder effect. Melle et al. (1991) found the same mutation on the background of RFLP haplotype 7 in patients from northeastern France or Belgium.

Apold et al. (1993) compiled data on the frequency of the G272X mutation in European populations. The mutation occurs north of the Alps and has a particularly high frequency in the Oslo Fjord region of Norway with the adjacent Bohuslan region of Sweden. An intermediate frequency was noted in the eastern part of Germany with the adjacent western part of Czechoslovakia. Genealogic studies revealed no common source for this mutation, but there was some geographic convergence to the Bohuslan region. The findings suggested a single origin for this mutation, with at least one founding population in southeastern Norway/adjacent Sweden.