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Mutation analysis of the PAH gene in Ukrainian population, a report from west Ukraine region

Makukh H.V., Chorna L.B., Tyrkus M.Ya., Akopyan H.R., Shuvarska V.I., Malakhova A.Y., Poliakova Ye.O.


SUMMARY. Phenylketonuria (PKU) is one of the most common autosomal recessive diseases caused by inherited defect in phenylalanine hydroxylase (PAH) that impairs po-stnatal cognitive development. Mutations in the PAH gene lead to complete or partial loss of PAH enzyme activity which cause to increasing phenylalanine se-rum level and phenotypic manifestations of PKU. In order to determine the PAH mutations spectrum in the population from the West region of Ukraine, 158 unrelated PKU patients were studied. 101 patients with hyperphenylalaninemia (HPA) were selected during the neonatal screening program. DNA from peripheral blood leukocytes was isolated and purified using a modified salting out method. A total of 316 alleles were studied by means of restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR, ACRS-PCR) method. The most prevalent mutation was R408W, occurring in 58.54 % of all alleles, with a very high degree of homozygosity (35.44 %). The frequencies of remaining identified mutations were: IVS10nt-11G>A (4.35 %), R158Q (4.17 %), Y414C (2.78 %) and R252W (1.25 %). The most common mutation in patients with PKU from the West region of Ukraine is R408W. The spectrum and frequency of mutations are correlated with the frequency in the general population of Ukraine and corresponded to the mutation spectrum in Eastern Europe.

Key words: hyperphenylalaninemia, mutation, phenylalanine hydroxylase gene (PAH), phenylketonuria

Tsitologiya i Genetika 2021, vol. 55, no. 5, pp. 13-19

  • State Institution Institute of Hereditary Pathology of National Academy of Medical Sciences of Ukraine, 31-a, M. Lysenko Str., Lviv, Ukraine, 79008

E-mail: makukh.h

Makukh H.V., Chorna L.B., Tyrkus M.Ya., Akopyan H.R., Shuvarska V.I., Malakhova A.Y., Poliakova Ye.O. Mutation analysis of the PAH gene in Ukrainian population, a report from west Ukraine region, Tsitol Genet., 2021, vol. 55, no. 5, pp. 13-19.

In "Cytology and Genetics":
H. V. Makukh, L. B. Chorna, M. Ya. Tyrkus, H. R. Akopyan, V. I. Shuvarska, A. Y. Malakhova & Ye. O. Poliakova Analysis of the PAH Gene Mutations in the Ukrainian Population: A Report from the West Ukrainian Region, Cytol Genet., 2021, vol. 55, no. 5, pp. 414419
DOI: 10.3103/S0095452721050066


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