Molecular analysis of PKU in Ireland.

[classical phenylketonuria]

Classical phenylketonuria (PKU : McKusick No . 261600 ) is caused by mutations occurring at the phenylalanine hydroxylase (PAH ) locus on chromosome 12 and has a prevalence in Ireland of 1 in 4500 . We examined 304 independent alleles from 350 patients for the presence of six mutations and have characterized VNTR alleles within the minisatellite region 3 ' to the PAH gene in patients carrying the most prevalent mutation . R 408 W was the most common mutation found , with a relative frequency of 42 %. All other mutations had relative frequencies of < 10 %. VNTR analysis showed that the R 408 W mutation is associated with the VNTR-8 allele in the Irish population , indicating that R 408 W is associated with RFLP haplotype 1 . This differs from that reported from eastern Europe where R 408 W is associated with RFLP haplotype 2 /VNTR-3 ; an observation which has led several groups to propose a Balto -Slavic origin for this mutation . These results support the hypothesis of a second , independent founding event for the R 408 W mutation on an RFLP haplotype 1 VNTR-8 chromosome background in the Irish /Celtic population .