Mutation Analysis of The Phenylalanine Hydroxylase Gene in Phenylketonuria Patients from Different Regions of Azerbaijan

Abstract

The present study aimed to determine frequencies of mutations in the phenylalanine hydroxylase gene (PAH) in 30 patients diagnosed with phenylketonuria, from 633 person who presented to Scientific Research Pediatric Institute of the Ministry of Health of Azerbaijan and hospitals of different regions of Azerbaijan over the period from 2016 to 2020. More than 600 mutations in the PAH gene in exons 6, 7, 8, 11 and 12 have been detected in various countries around the world. Among them, 18 different mutations were found in Azerbaijani patients (V245V, R261Q, Q232Q, V245V, P281L, R241C, L385L, V399V, E280K, R261X, A434D, R176X, Ex6-96A> G, R241C, R243Q, R256Q). The R261Q mutation in exon 7 was observed in seven patients from 30 patients. In this study, we identified mutations in the PAH gene and to evaluate the genetic heterogeneity of PKU disease in 30 Azerbaijanian patients who had been referred to Lankaran, Masalli (Southern region of Azerbaijan), Qabala, Oguz, Zagatala, Balakan (North-western region of Azerbaijan), Guba, Gusar, Khachmaz and Khudat (Northern region of Azerbaijan) regions. From this experiment, 7 of 30 PKU patients had the same mutation. Our analysis of the R261Q mutations was nearly similar to that observed in Southern region of Azerbaijan. The R261Q mutation in exon 7 with a relative frequency of 23.3 % is G → A substitution leads to conservation of arginine amino acid to glutamine amino acid at codon 782 of PAH. The another major mutation in our study was R241C (10%), which is similar to the data obtained in population of Northern region of Azerbaijan, R243Q (6.6%) and R252Q (6.6%). Studies have shown that this mutation is most common in the Azerbaijani population. Genetic drift and founder effect may have also played a role in the mutation spectrum we observed. The data obtained in our study can also be used in the development of genetic tests for phenylketonuria. Phenylketonuria (PKU) is an autosomal recessive genetic disease, caused by the phenylalanine hydroxylase (PAH) deficiency in the metabolic pathway, which prevents phenylalanine from being converted into tyrosine, leading to a large amount of phenylalanine discharged from the urine. Therefore, it is necessary to establish a simple, fast, accurate and reliable PKU molecular diagnostic method for clinical diagnosis.