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

IF 1.7 Q2 MEDICINE, GENERAL & INTERNAL
International Journal of Preventive Medicine Pub Date : 2024-07-17 eCollection Date: 2024-01-01 DOI:10.4103/ijpvm.ijpvm_50_23
Hossein Jalali, Daniel Zamanfar, Muhammad Amirzadegan, Farshide Ghadami, Mahan Mahdavi, Mohammad Reza Mahdavi
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引用次数: 0

摘要

背景:导致苯丙酮尿症(PKU)的苯丙氨酸羟化酶(PAH)基因中存在 1100 多种不同的致病变异体,这些变异体在不同种族群体中的分布也不尽相同。本研究旨在确定伊朗北部马赞达兰省和戈勒斯坦省的 PKU 患者中 PAH 基因全部 13 个外显子中致病变异的频率:40名来自马赞达兰省和戈勒斯坦省的无亲属关系的PKU患者参加了研究。使用Qiagen DNA提取试剂盒从白细胞中提取基因组DNA,并采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)和桑格测序法检测变异。对于新变异,则使用 InterVar 在线工具(PMID:28132688)对变异进行分类:结果:在 40 名接受调查的患者中观察到 21 个不同的致病变异。c.106611G>A变异在该地区的频率最高(27.5%),c.168+5G>C、c.473G>A和c.782 G>A变异是其他最常见的变异,等位基因频率分别为7.5%、5%和5%。在调查的患者中观察到三个新的致病变异,包括c.773T>G、c.878 T>C和c.1245del变异:结论:PAH 基因致病变异在各民族中的出现为了解该病的发病机制提供了宝贵的数据,有助于产前诊断项目的开展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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来源期刊
International Journal of Preventive Medicine
International Journal of Preventive Medicine MEDICINE, GENERAL & INTERNAL-
CiteScore
3.20
自引率
4.80%
发文量
107
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.
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