Molecular-Genetic Study of Phenylketonuria in Patients from Georgia
- Авторы: Gundorova P.1, Kuznetsova I.1, Agladze D.2, Margvelashvili L.3, Kldiashvili E.4, Kvlividze O.4,5, Kutsev S.1, Polyakov A.1
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Учреждения:
- Research Centre for Medical Genetics
- Research Institute of Clinical Medicine
- Childrens New Hospital
- New Vision University
- Georgian Foundation for Genetic and Rare Diseases
- Выпуск: Том 55, № 8 (2019)
- Страницы: 1025-1032
- Раздел: Human Genetics
- URL: https://journals.rcsi.science/1022-7954/article/view/189513
- DOI: https://doi.org/10.1134/S1022795419080064
- ID: 189513
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Аннотация
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.
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Об авторах
P. Gundorova
Research Centre for Medical Genetics
Автор, ответственный за переписку.
Email: p_gundorova@inbox.ru
Россия, Moscow, 115522
I. Kuznetsova
Research Centre for Medical Genetics
Email: p_gundorova@inbox.ru
Россия, Moscow, 115522
D. Agladze
Research Institute of Clinical Medicine
Email: p_gundorova@inbox.ru
Грузия, Tbilisi, 0112
L. Margvelashvili
Childrens New Hospital
Email: p_gundorova@inbox.ru
Грузия, Tbilisi, 0159
E. Kldiashvili
New Vision University
Email: p_gundorova@inbox.ru
Грузия, Tbilisi, 0159
O. Kvlividze
New Vision University; Georgian Foundation for Genetic and Rare Diseases
Email: p_gundorova@inbox.ru
Грузия, Tbilisi, 0159; Tbilisi, 0162
S. Kutsev
Research Centre for Medical Genetics
Email: p_gundorova@inbox.ru
Россия, Moscow, 115522
A. Polyakov
Research Centre for Medical Genetics
Email: p_gundorova@inbox.ru
Россия, Moscow, 115522