ABSTRACT
Analysis of the polymorphic variable number of tandem repeats [VNTR] is a powerful tool for detection of DNA variation among normal individuals within a population, as well as testing linkage to disease-underlying mutations in various ethnic groups. Phenylketonuria [PKU] is caused by mutations in the phenylalanine hydroxylase [PAH] gene, which has a VNTR region at the 3 end. In this work, we report on the PAH VNTR polymorphism patterns among a sample of the Egyptian population and a large number of PKU cases. The study included 77 normal subjects and 87 phenylketonuric probands. Genomic DNA was extracted from leukocytes using the salting out technique. DNA amplification using specific primers and the polymerase chain reaction was used to detect the various VNTR patterns. The VNTR heterozygosity index was 56% and 21% in the normal and PKU groups, respectively. The VNTR homozygosity index was comparably high in patients with IVS10-11 G>A and R261Q mutations, [i.e. > 80%]. An unusually high prevalence of the 8-RU and 10-RU alleles among non-IVS1011 G>A/non-R261Q PKU cases was noted. The VNTR patterns in both normal and PKU-affected Egyptians were highly heterogeneous. Moreover, both IVS10-11 G>A and R261Q showed previously unreported VNTR patterns. In conclusion, the study of PAH VNTR allele patterns among normal and PKU-affected Egyptian subjects has confirmed the high heterogeneity of the normal Egyptian population as well as the PKU patients