MOLECULAR ANALYSIS OF PKU IN IRELAND

Classical phenylketonuria (PKU: McKusick No. 261600) is caused by muta tions occurring at the phenylalanine hydroxylase (PAH) locus on chromo some 12 and has a prevalence in Ireland of 1 in 4500. We examined 304 independent alleles from 350 patients for the presence of six mutation s and have characterized VNTR;alleles within the minisatellite region 3' to the PAH gene in patients carrying the most prevalent mutation. R 408W was the most common mutation found, with a relative frequency of 42%. All other mutations had relative frequencies of <10%. VNTR analys is showed that the R408W mutation is associated with the VNTR-X allele in the Irish population, indicating that R408W is associated with RFL P haplotype 1. This differs from that reported from eastern Europe whe re R408W is associated with RFLP haplotype 2/VNTR-3; an observation wh ich has led several groups to propose a Balto-Slavic origin for this m utation. These results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR-8 c hromsome background in the Irish/Celtic population.