Fishchuk Liliya, Rossokha Zoia, Olkhovich Natalia, Pichkur Nataliia, Popova Olena, Medvedieva Nataliia, Vershyhora Viktoriia, Dubitska Olha, Shkurko Tetiana, Popovych Larysa, Bondar Olga, Morozuk Irina, Onyshchenko Svitlana, Yevtushok Lyubov, Tsizh Oksana, Bryl Iryna, Tul Olena, Kalynka Svitlana, Zinkina Iryna, Matviiuk Svitlana, Riabova Yulianna, Gorovenko Nataliia
SI "Reference-centre for molecular diagnostic of Public Health Ministry of Ukraine", Kyiv, Ukraine.
Institute of Genetic and Regenerative Medicine NAMS of Ukraine, Kyiv, Ukraine.
Mol Genet Metab Rep. 2022 Aug 1;32:100907. doi: 10.1016/j.ymgmr.2022.100907. eCollection 2022 Sep.
Phenylketonuria (PKU) is hyperphenylalaninemia that develops due to a deficiency of the phenylalanine hydroxylase enzyme (PAH). Identification of variants in the gene is necessary for verification of the diagnosis, choice of treatment tactics, detection of heterozygous carriers. The aim of the study was to analyze the effectiveness of identification of selected pathological variants in the gene during the newborn screening program. This study relied on the results of the examination of 257 patients (138 boys and 119 girls) with hyperphenylalaninemia from different regions of Ukraine. Genotyping was performed on nine pathogenic variants in gene: I65T, R261Q, G272*, R252W, R261*, R408W, IVS12 + 1G > A, Y414C, IVS10-11G > A. According to the results of the study, variants R408W (AF = 52.7%), R252W (AF = 3.5%) and Y414C (AF = 1.8%) were the most common. More than half of the examined patients (51.7%) had a compound genotype with a major variant of R408W in one allele. Approximately a quarter of the examined patients (26.8%) had the R408W/R408W genotype. In 12.1% of patients, the applied panel of variants of the gene did not allow us to identify the pathogenic variant in any allele. We conclude that the selected panel allowed us to identify the presence of variants in 87.9% of patients with PKU. The panel of genetic testing in the gene for the newborns that we used for the study allows accurate prediction of some phenotypes for therapy planning. But in-depth analysis of pathological gene variants may be necessary for unclear and difficult cases of the disease, and for genetic counseling of patients families.
苯丙酮尿症（PKU）是由于苯丙氨酸羟化酶（PAH）缺乏而导致的高苯丙氨酸血症。鉴定该基因中的变异对于确诊、治疗策略的选择以及杂合子携带者的检测至关重要。本研究的目的是分析在新生儿筛查项目中鉴定该基因选定病理变异的有效性。本研究基于对来自乌克兰不同地区的257例高苯丙氨酸血症患者（138名男孩和119名女孩）的检查结果。对该基因的9个致病变异进行了基因分型：I65T、R261Q、G272*、R252W、R261*、R408W、IVS12 +1G>A、Y414C、IVS10 - 11G>A。根据研究结果，变异R408W（等位基因频率AF = 52.7%）、R252W（AF = 3.5%）和Y414C（AF = 1.8%）最为常见。超过一半的受检患者（51.7%）具有复合基因型，其中一个等位基因存在主要变异R408W。约四分之一的受检患者（26.8%）具有R408W/R408W基因型。在12.1%的患者中，所应用的该基因变异检测组合无法在任何一个等位基因中鉴定出致病变异。我们得出结论，选定的检测组合使我们能够在87.9%的PKU患者中鉴定出变异的存在。我们在研究中用于新生儿的该基因基因检测组合能够准确预测一些用于治疗规划的表型。但对于病情不明确和复杂的病例以及患者家庭的遗传咨询，可能需要对病理基因变异进行深入分析。
