Molecular-Genetic Study of Phenylketonuria in Patients from Georgia
- Authors: Gundorova P.1, Kuznetsova I.A.1, Agladze D.2, Margvelashvili L.3, Kldiashvili E.4, Kvlividze O.4,5, Kutsev S.I.1, Polyakov A.V.1
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Affiliations:
- Research Centre for Medical Genetics
- Research Institute of Clinical Medicine
- Childrens New Hospital
- New Vision University
- Georgian Foundation for Genetic and Rare Diseases
- Issue: Vol 55, No 8 (2019)
- Pages: 1025-1032
- Section: Human Genetics
- URL: https://journals.rcsi.science/1022-7954/article/view/189513
- DOI: https://doi.org/10.1134/S1022795419080064
- ID: 189513
Cite item
Abstract
A molecular-genetic study of the full mutation spectrum in phenylketonuria (PKU) in patients from Georgia was conducted for the first time. The frequency of PKU according to neonatal screening over 15 years was 1 : 6111 newborns. One hundred forty probands diagnosed with phenylketonuria were examined. The following methods were used: detection of 25 frequent mutations in the PAH gene, next generation sequencing of the PAH, PTS, GCH1, PCBD1, QDPR, SPR, and DNAJC12 genes, and the MLPA method for search for large deletions and duplications. The most frequent pathogenic variants identified during the study were p.Pro281Leu (33.7%), IVS10-11G>A (21.1%), and p.Arg261* (8.6%). Mutations were found on 97.8% of the chromosomes studied. Two pathogenic variants were identified in 135 probands (96.4%); the diagnosis of phenylketonuria was confirmed. According to the results of the prediction of a potential response to the sapropterin therapy based on the genotype, the absence of therapy response would be observed in 70% of probands. No patients with BH4-dependent forms of hyperphenylalaninemia were found in this study.
Keywords
About the authors
P. Gundorova
Research Centre for Medical Genetics
Author for correspondence.
Email: p_gundorova@inbox.ru
Russian Federation, Moscow, 115522
I. A. Kuznetsova
Research Centre for Medical Genetics
Email: p_gundorova@inbox.ru
Russian Federation, Moscow, 115522
D. Agladze
Research Institute of Clinical Medicine
Email: p_gundorova@inbox.ru
Georgia, Tbilisi, 0112
L. Margvelashvili
Childrens New Hospital
Email: p_gundorova@inbox.ru
Georgia, Tbilisi, 0159
E. Kldiashvili
New Vision University
Email: p_gundorova@inbox.ru
Georgia, Tbilisi, 0159
O. Kvlividze
New Vision University; Georgian Foundation for Genetic and Rare Diseases
Email: p_gundorova@inbox.ru
Georgia, Tbilisi, 0159; Tbilisi, 0162
S. I. Kutsev
Research Centre for Medical Genetics
Email: p_gundorova@inbox.ru
Russian Federation, Moscow, 115522
A. V. Polyakov
Research Centre for Medical Genetics
Email: p_gundorova@inbox.ru
Russian Federation, Moscow, 115522