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Mutations in gene ATP7B in ukrainian patients with high risk of Wilsons disease

Makukh H., Hayboniuk I., Zarina A., Semeriak O.M., Gailite L.

 




SUMMARY. SI Institute of Hereditary Pathology of Ukrainian National Academy of Medical Wilsons disease (WD) is an autosomal recessive con-dition, caused by the impaired metabolism of copper due to hereditary mutations in the gene ATP7, the spectrum and frequency of mutations are considerably different in different populations. To define the list of the most frequent mutations in the gene ATP7B in patients from Ukraine with the purpose of introducing the genetic testing into the practice of medical and genetic consulting. The materials for the study were DNA samples, isolated from leukocytes of 90 patients (41 males and 49 females), aged 360, with clinical and biochemical signs of the disease. The molecular and genetic analysis of the mutation c.3207C > A (H1069Q), the most common among Europeans, was conducted by the method of PCR Bi-PASA. The sequencing of exons of the gene ATP7B was conducted for 23 patients, who had scored 3 by the Leipzig scoring system. The molecular and genetic analysis of the mutations in the gene ATP7B verified Wilsons disease genetically in 23.3 % of patients with clinical signs of the disease. Five different mutations and five single-nucleotide polymorphisms in the gene ATP7B were determined in the patients of the investigated sampling. The mutation (c.3207C > A), most common for Europeans, was determined in 28 patients, including 15 cases of homozygosity. In 6 cases the mutation c.3207C > A was in compound heterozygous state with other mutations in the gene ATP7B: 3 c.2304dupC (8 exon), 1 c.2128G > A (8 exon), 1 c.3011A > C (13 exon), 1 c.3402delC (15 exon). No other transformations, except for mutation H1069Q, were found in 7 persons. The frequency of the pathogenic allele c.3207C > A (H1069Q) of the gene ATP7B, most widespread in Europe, among patients who scored 3 and more points according to the scoring system of diagnostic tests, was 76.8 %. The frequency of allele c.2304dupC among genetically verified cases was 7 %. The genetic testing of two mutations in the gene ATP7B (c.3207C > A and c.2304dupC), which are frequent among patients with Wilsons disease from Ukraine, was introduced into practice. The third of patients did not have pathogenic alleles in exon sequences of the gene ATP7B but had one or several single nucleotide polymorphisms, including several non-pathogenic variants and one polymorphism associated with the increased risk of developing Alzheimers disease (c.2495A > G). The obtained results indicate high informative value of genetic testing of mutations c.3207C > A and c.2304dupC in the gene ATP7B among Ukrainian patients with Wilsons disease.

Key words: ATP7B gene, mutation, Wilson disease, Ukraine

Tsitologiya i Genetika 2020, vol. 54, no. 4, pp. 53-62

  1. SI Institute of Hereditary Pathology of Ukrainian National Academy of Medical Science, 31-a, Lysenko str., Lviv, Ukraine
  2. Riga Stradins University, 16 Dzirciema str., Riga, Latvia, LV-1007
  3. KI LOR Lviv Regional Clinical Hospital, 4, Nekrasova str., Lviv, Ukraine, 79008

E-mail: makukh.h ihp.lviv.ua, ivankagaiboniuk gmail.com, zarina.agnese gmail.com, dr.orchyk gmail.com, linda.gailite rsu.lv

Makukh H., Hayboniuk I., Zarina A., Semeriak O.M., Gailite L. Mutations in gene ATP7B in ukrainian patients with high risk of Wilsons disease, Tsitol Genet., 2020, vol. 54, no. 4, pp. 53-62.

In "Cytology and Genetics":
H. Makukh, I. Hayboniuk, A. Zarina, O. M. Semeriak & L. Gailite Mutations in the ATP7B Gene in Ukrainian Patients with High Risk of Wilsons Disease, Cytol Genet., 2020, vol. 54, no. 4, pp. 324332
DOI: 10.3103/S009545272004009X


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