Mutation Analysis of PAH Gene in Phenylketonuria Patients from the North of Iran: Identification of Three Novel Pathogenic Variants

International Journal of Preventive Medicine (Int J Prev Med)2008-780215420240811Mutation Analysis of PAH Gene in Phenylketonuria Patients from the North of Iran: Identification of Three Novel Pathogenic Variants2327ENThalassemia Research Center, Hemoglobinopathies Institute, Mazandaran University of Medical Sciences, SariDiabetes Research Center, Mazandaran University of Medical Sciences, SariSinaye Mehr Research Center, SariSinaye Mehr Research Center, SariSinaye Mehr Research Center, SariThalassemia Research Center, Hemoglobinopathies Institute, Mazandaran University of Medical Sciences, Sari20240724Background: There are more than 1100 different pathogenic variants in the phenylalanine hydroxylase (PAH) gene that are responsible for phenylketonuria (PKU) diseases, and the spectrum of these mutations varies in different ethnic groups. The aim of the present study was to identify the frequency of pathogenic variants in all 13 exons of the PAH gene among patients with PKU in Mazandaran and Golestan provinces in the north of Iran. Methods: Forty unrelated PKU patients from Mazandaran and Golestan provinces were enrolled in the study. Genomic DNA was extracted from leukocytes using a Qiagen DNA extraction kit and polymerase chain reaction – restriction fragment length polymorphism (PCR‑RFLP), and Sanger sequencing methods were applied to detect the variants. In the case of new variants, the InterVar online tool (PMID: 28132688) was used to classify the variants. Results: Twenty‑one different pathogenic variants were observed among the 40 investigated patients. The c.106611G>A variant had the highest frequency (27.5%) in the region, and the c.168+5G>C, c.473G>A, and c.782 G>A variants were the other most frequent mutations with allelic frequencies of 7.5, 5, and 5%, respectively. Three novel pathogenic variants including c.773T>G, c.878 T>C, and c. 1245del variants were observed among the investigated patients. Conclusions: The introduction of pathogenic variants in the PAH gene in each ethnic group provides valuable data regarding the understanding of the pathogenesis of the disease and can be helpful for prenatal diagnosis programs. <span class="ej-journal-name" style="box-sizing: inherit; font-style: italic; font-weight: 500; color: #3b3030; font-family: 'Fira Sans', sans-serif; font-size: 14px; font-variant-ligatures: normal; font-variant-caps: normal; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial;">International Journal of Preventive Medicine <span id="ej-journal-date-volume-issue-pg" style="box-sizing: inherit; color: #3b3030; font-family: 'Fira Sans', sans-serif; font-size: 14px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial;"><a style="box-sizing: border-box; color: #005b92; text-decoration: none; background-color: transparent; cursor: pointer; outline: 0px;" href="https://journals.lww.com/ijom/pages/currenttoc.aspx">15():22, April 2024.</a><span style="box-sizing: inherit; color: #3b3030; font-family: 'Fira Sans', sans-serif; font-size: 14px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial;"> | <span class="ej-journal-doi" style="box-sizing: inherit; font-style: italic; font-weight: 500; color: #3b3030; font-family: 'Fira Sans', sans-serif; font-size: 14px; font-variant-ligatures: normal; font-variant-caps: normal; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial;">DOI: <span style="color: #3b3030; font-family: 'Fira Sans', sans-serif; font-size: 14px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400; letter-spacing: normal; orphans: 2; text-align: start; text-indent: 0px; text-transform: none; widows: 2; word-spacing: 0px; -webkit-text-stroke-width: 0px; white-space: normal; background-color: #ffffff; text-decoration-thickness: initial; text-decoration-style: initial; text-decoration-color: initial; display: inline !important; float: none;">10.4103/ijpvm.ijpvm_50_23Corresponding Author: Dr. Mohammad Reza MahdaviE‑mail: Mahdavi899@gmail.comYou can also search for this author in: <a title="PubMed" href="https://pubmed.ncbi.nlm.nih.gov/?term=%28Mazandaran+University+of+Medical+Sciences%5BAffiliation%5D%29+AND+%28Mohammad+Reza+Mahdavi+Amiri%5BAuthor%5D%29&sort=">PubMed</a> <a title="Google Scholar" href="https://scholar.google.com/citations?hl=en&user=FUd2sf0AAAAJ">Google Scholar</a>http://ijpm.mui.ac.ir/index.php/ijpm/article/view/2911http://ijpm.mui.ac.ir/index.php/ijpm/article/download/2911/717718752