Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the PAH Gene

Inna S Tebieva; Polina V Mishakova; Yulia V Gabisova; Alana V Khokhova; Tamara G Kaloeva; Andrey V Marakhonov; Olga A Shchagina; Alexander V Polyakov; Evgeny K Ginter; Sergey I Kutsev; Rena A Zinchenko

doi:10.3390/ijms25094598

Genetic Landscape and Clinical Features of Hyperphenylalaninemia in North Ossetia-Alania: High Frequency of P281L and P211T Genetic Variants in the PAH Gene

Int J Mol Sci. 2024 Apr 23;25(9):4598. doi: 10.3390/ijms25094598.

Affiliations

¹ North-Ossetian State Medical Academy, 362003 Vladikavkaz, Russia.
² Republican Children's Clinical Hospital, 362003 Vladikavkaz, Russia.
³ Research Centre for Medical Genetics, 115522 Moscow, Russia.

Abstract

This study, conducted in the Republic of North Ossetia-Alania (RNOA), aimed to explore the genetic landscape of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) in the Ossetian population using data from newborn screening (NBS). Through comprehensive molecular genetic analysis of 29 patients with HPA from diverse ethnic backgrounds, two major genetic variants in the PAH gene, P281L and P211T, were identified, constituting 50% of all detected pathogenic alleles in Ossetian patients. Remarkably, these variants exhibited an exceptionally high frequency in the Ossetian population, surpassing global prevalence rates. This study unveiled a notable prevalence of mild forms of HPA (78%), underscoring the importance of genetic counseling for carriers of pathogenic variants in the PAH gene. Moreover, the findings emphasized the necessity for ongoing monitoring of patients with mild forms, as they may lack significant symptoms for diagnosis, potentially impacting offspring. Overall, this research offers valuable insights into the genetic landscape of HPA and PKU in the Ossetian population.

Keywords: Ossetian population; PAH gene; Republic of North Ossetia-Alania; frequent mutations; hyperphenylalaninemia; phenylketonuria.

MeSH terms

Alleles
Female
Gene Frequency
Humans
Infant, Newborn
Male
Neonatal Screening
Phenylalanine Hydroxylase* / genetics
Phenylketonurias* / epidemiology
Phenylketonurias* / genetics

Substances

Phenylalanine Hydroxylase

Grants and funding

This work was funded by a state assignment of the Ministry of Science and Higher Education of the Russian Federation. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of this manuscript, or in the decision to publish the results.