Hossein Jalali, Daniel Zamanfar, Muhammad Amirzadegan, Farshide Ghadami, Mahan Mahdavi, Mohammad Reza Mahdavi
{"title":"伊朗北部苯丙酮尿症患者 PAH 基因突变分析:鉴定三种新型致病变异基因","authors":"Hossein Jalali, Daniel Zamanfar, Muhammad Amirzadegan, Farshide Ghadami, Mahan Mahdavi, Mohammad Reza Mahdavi","doi":"10.4103/ijpvm.ijpvm_50_23","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There are more than 1100 different pathogenic variants in the phenylalanine hydroxylase (<i>PAH</i>) 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 <i>PAH</i> gene among patients with PKU in Mazandaran and Golestan provinces in the north of Iran.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The introduction of pathogenic variants in the <i>PAH</i> 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.</p>","PeriodicalId":14342,"journal":{"name":"International Journal of Preventive Medicine","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338363/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mutation Analysis of PAH Gene in Phenylketonuria Patients from the North of Iran: Identification of Three Novel Pathogenic Variants.\",\"authors\":\"Hossein Jalali, Daniel Zamanfar, Muhammad Amirzadegan, Farshide Ghadami, Mahan Mahdavi, Mohammad Reza Mahdavi\",\"doi\":\"10.4103/ijpvm.ijpvm_50_23\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There are more than 1100 different pathogenic variants in the phenylalanine hydroxylase (<i>PAH</i>) 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 <i>PAH</i> gene among patients with PKU in Mazandaran and Golestan provinces in the north of Iran.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>The introduction of pathogenic variants in the <i>PAH</i> 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.</p>\",\"PeriodicalId\":14342,\"journal\":{\"name\":\"International Journal of Preventive Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338363/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Preventive Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.4103/ijpvm.ijpvm_50_23\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Preventive Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4103/ijpvm.ijpvm_50_23","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Mutation Analysis of PAH Gene in Phenylketonuria Patients from the North of Iran: Identification of Three Novel Pathogenic Variants.
Background: 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.
期刊介绍:
International Journal of Preventive Medicine, a publication of Isfahan University of Medical Sciences, is a peer-reviewed online journal with Continuous print on demand compilation of issues published. The journal’s full text is available online at http://www.ijpvmjournal.net. The journal allows free access (Open Access) to its contents and permits authors to self-archive final accepted version of the articles on any OAI-compliant institutional / subject-based repository. The journal will cover technical and clinical studies related to health, ethical and social issues in field of Preventive Medicine. Articles with clinical interest and implications will be given preference.