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

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.