Abstract Phenylketonuria (PKU) is one of the most frequent autosomal recessive diseases caused by inherited deficiency of phenylalanine hydroxylase (PAH), which is accompanied by intellectual disability. The PAH gene mutations lead to a complete or partial loss of activity in the PAH enzyme, resulting in an increase in the serum phenylalanine level and phenotypic PKU manifestations. The study includes an analysis of the spectrum of PAH mutations among patients with PHU from West Ukrainian regions. Molecular genetic analyses were performed in 158 nonrelative PKU patients, including a cohort of 101 patients with hyperphenylalaninemia (HPA) diagnosed by neonatal screening. DNA of the PKU patients was isolated by the salting-out method from peripheral blood lymphocytes. We used the method of polymerase chain reaction with restriction fragment length polymorphism (RFLP–PCR, ACRS–PCR) to study 316 alleles. According to the results of the study, the R408W mutation has been identified with high degree homozygosity (35.44%) in 58.54% of mutant alleles. The frequencies of other identified mutations were as follows (in parentheses): IVS10nt-11G>A (4.35%), R158Q (4.17%), Y414C (2.78%), and R252W (1.25%). The most spread mutation among PKU patients from the western region of Ukraine was R408W. The spectrum and the frequency of mutations in the studied sample correlated with the frequency shown by the general population of Ukraine and corresponded to the spectrum of mutations in Western Europe.
Keywords: phenylalanine hydroxylase (PAH) gene hyperphenylalaninemia mutation phenylketonuria
