A Comprehensive Study of Disease-Causing Variants in PAH, QDPR, PTS, and PCD Genes in Iranian Patients with Hyperphenylalaninemia: A Systematic Review.

IF 1.1 4区生物学 Q4 GENETICS & HEREDITY Human Heredity Pub Date : 2023-01-01 Epub Date: 2023-01-16 DOI:10.1159/000529037

Mahmoud Ghanei, Seyedeh Helia Sadat Fatemi, Tayebeh Hamzehlouei

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Abstract

Background: Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and clinical geneticists in differential diagnosis, appropriate prescription drugs, and saving time and cost. This study attempted to identify these genes' most prevalent disease-causing variants in Iranian HPA patients.

Summary: This study was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Before it started, the flow work and inclusion/exclusion criteria were published as a protocol in PROSPERO (CRD42021273705). We conducted a comprehensive search on December 10, 2022, on international online databases, including Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, Google Scholar, SID, ISC, and Magiran search engine, to find pertinent publications. Some studies were chosen based on inclusion and exclusion criteria. Altogether, 1,243 Iranian patients from 13 articles were considered. In total, we identified 129 distinct disease-causing variants in PAH (20 novel variants), 29 in QDPR (17 novel variants), 15 in PTS (seven novel variants), and one novel variant in PCD. Twenty disease-causing variants for PAH, 18 for QDPR, and 8 for PTS are included in the genes' proposed genetic diagnostic panels. These panels include more than 75% of the documented disease-causing variants in the Iranian population.

Key messages: The findings of this research illustrated the spectrum of disease-causing variants in the PAH, QDPR, PTS, and PCD genes identified in Iranian HPA patients. Common disease-causing variants of these genes may be chosen as a preliminary diagnostic panel for early diagnosis and lowering therapy costs.

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伊朗高苯丙氨酸血症患者中 PAH、QDPR、PTS 和 PCD 基因致病变异的综合研究：系统回顾

背景：高苯丙氨酸血症（HPA）是一种常染色体隐性遗传疾病，由苯丙氨酸羟化酶（PAH）缺乏或负责辅因子四氢生物蝶呤（BH4）的生物合成或再生的基因缺陷引起，包括 GCH1、SR、QDPR、PTS 和 PCD。鉴定这些基因中的致病变异体有助于医生和临床遗传学家进行鉴别诊断、对症下药并节省时间和成本。本研究试图确定这些基因在伊朗 HPA 患者中最普遍的致病变异。摘要：本研究根据系统综述和荟萃分析首选报告项目（PRISMA）指南进行。在研究开始之前，研究流程和纳入/排除标准已作为协议发布在 PROSPERO (CRD42021273705)上。我们于 2022 年 12 月 10 日在国际在线数据库（包括 Web of Science、Scopus、EMBASE、Science Direct、PubMed/Medline、Google Scholar、SID、ISC 和 Magiran 搜索引擎）中进行了全面搜索，以找到相关出版物。根据纳入和排除标准选择了一些研究。共考虑了 13 篇文章中的 1,243 名伊朗患者。我们总共发现了 129 个不同的 PAH 致病变异体（20 个新型变异体）、29 个 QDPR 致病变异体（17 个新型变异体）、15 个 PTS 致病变异体（7 个新型变异体）和 1 个 PCD 致病变异体。PAH 的 20 个致病变异体、QDPR 的 18 个致病变异体和 PTS 的 8 个致病变异体已被纳入基因的拟议基因诊断面板中。这些基因组包括了伊朗人口中超过 75% 已记录的致病变体：本研究结果说明了在伊朗 HPA 患者中发现的 PAH、QDPR、PTS 和 PCD 基因致病变异的范围。可选择这些基因中的常见致病变异作为初步诊断面板，以进行早期诊断并降低治疗成本。

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来源期刊

Human Heredity 生物-遗传学

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.