165 MOLECULAR ANALYSIS OF PKU HAPLOTYPES IN THE POPULATION OF SOUTHERN POLAND

Abstract

Out of a population of 138598 infants born in Southern Poland between 1987 through 1989, and screend for PKU, 22 cases were ascertained. DNA from 22 probands and their parents was isolated from peripheral blood leukocytes. Eight restriction enzymes were used (Bgl II, Pvu II, Eco RI, Msp I, Xmn I, Hind III and Eco RV). Polymorphic restriction sites were analyzed with the cDNA probe pH PAH 247. The mutation of codon 408 (exon 12, C … T, Arg … Trp) was tested on amplified DNA by dot-blot hybridization with 32P - labeled allele -specific oligonucleotides. Eight RFLP sites of the PAH gene were defined in 88 parental chromosomes, revealing 21 different haplotypes (HT). Among those, 16 have been already described, 5 - represented the new ones. The most common HT among those carrying normal alleles were: HT1 (27.3%) and HT4 (11.4%). Within the group of HT with mutant allele the most frequent was HT2 (56.8%) whereas the frequency of the same HT in French, Danish and German populations ranged from 12% to 24%. HT3, being the most common in Danish (38%) and relatively frequent in other western European populations (13-14%) appeared to be very rare in our sample (2.3%). The mutation in codon 408 was found in 25 out of 44 probands' chromosomes. Only one mutation was carried by HT5, the remaining 24 were associated with HT2. Our results confirm molecular heterogeneity of PKU haplotypes, as well as their significant interpopulation variation.

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