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The Frequency of Heterozygous Carriage of the PAH Gene Nucleotide Sequence Variants Associated with the Development of Phenylketonuria in the ESSE-Vologda Population-Based Cohort Study

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Abstract

The aim of the study was to develop a panel for detecting heterozygous carriage of frequent mutations associated with phenylketonuria (PKU), and to determine their allelic frequencies in one of the regions of Russia. PKU is one of the most common monogenic diseases with autosomal recessive inheritance. Carrier screening leads to a reduction in the number of children born with PKU. The diagnostic panel included 23 pathogenic variants of the PAH gene nucleotide sequence. Participants of the study (n = 642) were randomly selected from an ESSE-Vologda population-based study. Genotyping was performed using real-time polymerase chain reaction on a QuantStudio 12K Flex Real-Time PCR System (Thermo Fisher Scientific, United States). The data were analyzed using the TaqMan Genotyper Software (Thermo Fisher Scientific, United States). Seventeen heterozygous carriers of six variants of the nucleotide sequence associated with the development of PKU were identified: R408W (rs5030858), A403V (rs5030857), I306V (rs62642934), L48S (rs5030841), IVS12+1G>A (rs5030861), R261Q (rs5030849_C_T). The frequency of heterogyzotes in the Russian population was 2.65% (95% CI 1.55–4.21), or 1 : 38. The data obtained indicate the prospects of mass screening for the carriage of frequent mutations associated with PKU in people with an uncomplicated family history. The developed diagnostic panel allows one to rapidly obtain the result of genetic analysis and can be used for PKU carrier screening.

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Authors and Affiliations

  1. National Medical Research Center for Therapy and Preventive Medicine, Ministry of Health of the Russian Federation, 101990, Moscow, Russia

    O. V. Kurilova, M. V. Klimushina, A. V. Kiseleva, A. I. Ershova, E. A. Sotnikova, M. G. Divashuk, E. Yu. Khlebus, O. P. Skirko, I. A. Efimova, S. A. Shalnova, A. N. Meshkov & O. M. Drapkina

  2. Institute of Molecular Genetics, National Research Center “Kurchatov Institute”, 123182, Moscow, Russia

    P. A. Slominsky

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  1. O. V. Kurilova
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  2. M. V. Klimushina
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Correspondence to O. V. Kurilova.

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Conflict of interests. The authors declare that they have no conflicts of interest.

Statement of compliance with standards of research involving humans as subjects. This article does not contain any studies involving animals as subjects. All procedures in studies involving human participants were carried out in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants involved in the study.

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Translated by D. Novikova

ADDITIONAL INFORMATION

Kurilova O.V.: https://orcid.org/0000-0003-3082-5161; e‑mail: olga_kurilova81@mail.ru

Klimushina M.V.: https://orcid.org/0000-0002-7876-9325; e-mail: mklimushina@gmail.com

Kiseleva A.V.: https://orcid.org/0000-0003-4765-8021; e‑mail: sanyutabe@gmail.com

Ershova A.I.: https://orcid.org/0000-0001-7989-0760; e‑mail: alersh@mail.ru

Sotnikova E.A.: https://orcid.org/0000-0002-8395-4146; e-mail: sotnikova.evgeniya@gmail.com

Divashuk M.G.: https://orcid.org/0000-0001-6221-3659; e-mail: divashuk@gmail.com

Khlebus E.Yu.: https://orcid.org/0000-0002-8355-8960; e-mail: elkhlebus@gmail.com

Skirko O.P.: https://orcid.org/0000-0003-3755-0279; e‑mail: ops_70@mail.ru

Efimova I.A.: https://orcid.org/0000-0002-3081-8415; e‑mail: biobank@gnicpm.ru

Shalnova S.A.: https://orcid.org/0000-0003-2087-6483; e‑mail: sshalnova@gnicpm.ru

Slominsky P.A.: https://orcid.org/0000-0003-3530-0655; e-mail: paslominsky@bk.ru

Meshkov A.N.: https://orcid.org/0000-0001-5989-6233; e-mail: meshkov@lipidclinic.ru

Drapkina O.M.: https://orcid.org/0000-0002-4453-8430; e-mail: odrapkina@gnicpm.ru

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Kurilova, O.V., Klimushina, M.V., Kiseleva, A.V. et al. The Frequency of Heterozygous Carriage of the PAH Gene Nucleotide Sequence Variants Associated with the Development of Phenylketonuria in the ESSE-Vologda Population-Based Cohort Study. Mol. Genet. Microbiol. Virol. 36, 92–99 (2021). https://doi.org/10.3103/S0891416821020038

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