1Research Institute of Clinical Medicine, Tbilisi; 2School of Medicine, New Vision University; 4Pediatric Surgery Center (KidCo), Tbilisi; Georgia.
3Petre Shotadze Tbilisi Medical Academy, Georgia.
Georgian Med News. 2020 Nov(308):143-149.
The aim of the study was to compare Georgian PAH mutation spectrum to the most frequent European mutations. Population study publications were reviewed and 20 most frequent European PAH mutations were determined. Mutations were detected in 40 Georgian PKU patients using Sanger sequencing. PAH mutations were detected on all 80 alleles, clinical diagnose of PKU was confirmed in all 40 patients. Detected mutations in Georgian population was: P281L in 37.5%, IVS10-11G>A in 17.5%, R261X in 10%, L48S in 8.75%, E280K in 5%, R270K in 3.75%, E390G in 3.75% and mutations R252W, IVS12+1G>A, R243Q, R261Q, 1089delG, Y387H, EX5del, IVS7-5T>C, IVS12+1G>A, G171R, IVS2+5G>C each in 1.25%. Study revealed that the most common Georgian PAH mutations spectrum differs from the European one. 9 out of 18 detected mutations coincide with the European panel. At the same time more than half (55%) of the mutations found in Georgians were not identified as the most common mutations in Europe. These findings may indicate the necessity for the development of diagnostic panels specific to the Georgian population, including both 9 frequent European PAH mutations and 9 mutations more common for the Georgian population, which will significantly improve the quality of PKU diagnostics in Georgia. The results have been obtained are of an intermediate nature, which propose to continue and complete this research by studying the entire Georgian PKU population.
本研究旨在比较格鲁吉亚 PAH 突变谱与欧洲最常见的突变。对人群研究文献进行了回顾，并确定了 20 种最常见的欧洲 PAH 突变。使用 Sanger 测序在 40 名格鲁吉亚 PKU 患者中检测到突变。在所有 80 个等位基因中均检测到 PAH 突变，40 名患者的 PKU 临床诊断均得到确认。在格鲁吉亚人群中检测到的突变是：P281L 占 37.5%，IVS10-11G>A 占 17.5%，R261X 占 10%，L48S 占 8.75%，E280K 占 5%，R270K 占 3.75%，E390G 占 3.75%，以及 R252W、IVS12+1G>A、R243Q、R261Q、1089delG、Y387H、EX5del、IVS7-5T>C、IVS12+1G>A、G171R、IVS2+5G>C 各占 1.25%。研究表明，格鲁吉亚最常见的 PAH 突变谱与欧洲不同。在检测到的 18 种突变中，有 9 种与欧洲面板一致。与此同时，在格鲁吉亚发现的一半以上（55%）的突变未被确定为欧洲最常见的突变。这些发现可能表明需要针对格鲁吉亚人群开发特定的诊断面板，包括 9 种常见的欧洲 PAH 突变和 9 种在格鲁吉亚更为常见的突变，这将显著提高格鲁吉亚 PKU 诊断的质量。本研究结果为中间性质，建议通过研究整个格鲁吉亚 PKU 人群来继续和完成这项研究。
