Assessment of Pathogenic Variants in the PAH Gene and Genotype-Phenotype Correlation in Phenylketonuria Patients from Turkey.

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Özgür Balasar, Banu Kadıoğlu Yılmaz, Müşerref Başdemirci, Hatice Koçak Eker, Büşra Eser Çavdartepe, Levent Şimşek, Ebru Tunçez, Fahrettin Duymuş
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引用次数: 0

Abstract

This study aims to determine the allele and genotype frequency, evaluate genotype-phenotype correlation and contribute to the spectrum of pathogenic variants in the PAH gene. Ninety-three individuals diagnosed with PKU were included in the study. Next-generation sequencing was utilized for detecting variants in the PAH gene. Copy Number Variations in patients without biallelic pathogenic variant were investigated by Multiplex Ligation-dependent Probe Amplification method. Genotype-phenotype correlations and genotype-based phenotype predictions were examined by comparing molecular test results with BIOPKUdb database. The clinical distributions of the patients were as follows: classic PKU 21% (n = 19), mild PKU 3% (n = 3), and mild hyperphenylalaninemia 76% (n = 71), respectively. Thirty-nine distinct variants and 70 distinct genotypes were found in patients. The most frequently observed variant was p.(Ala300Ser) (13.9%) and the most frequently observed genotype was p.[Ala300Ser];[Ala300Ser] (5.6%). Compound heterozygous genotypes (%69) were more prevalent than homozygous genotypes. A novel variant, c.441+4A>C, was observed. Predicted metabolic phenotypes in the database showed consistency with patient phenotypes (n = 33/41). BH4 responsiveness showed partial consistency with database predictions (n = 13/25). Establishing genotype-phenotype correlations can facilitate personalized management approaches. Overall, this study contributes to understanding the genetic basis and clinical course of PKU.

土耳其苯丙酮尿症患者 PAH 基因致病变异及基因型与表型相关性评估
本研究旨在确定等位基因和基因型频率,评估基因型与表型之间的相关性,并对 PAH 基因致病变异谱做出贡献。研究共纳入了 93 名确诊为 PKU 的患者。研究利用新一代测序技术检测 PAH 基因的变异。采用多重连接依赖性探针扩增法对无双拷贝致病变异的患者的拷贝数变异进行了调查。通过将分子检测结果与 BIOPKUdb 数据库进行比较,研究了基因型与表型的相关性以及基于基因型的表型预测。患者的临床分布情况如下:典型 PKU 21%(n = 19)、轻度 PKU 3%(n = 3)和轻度高苯丙氨酸血症 76%(n = 71)。在患者中发现了 39 个不同的变体和 70 个不同的基因型。最常见的变异为 p.(Ala300Ser) (13.9%),最常见的基因型为 p.[Ala300Ser];[Ala300Ser] (5.6%)。复合杂合基因型(%69)比同源杂合基因型更常见。观察到一个新的变异,c.441+4A>C。数据库中预测的代谢表型与患者表型一致(n = 33/41)。BH4 反应性与数据库预测结果部分一致(n = 13/25)。建立基因型与表型之间的相关性可促进个性化管理方法。总之,这项研究有助于了解 PKU 的遗传基础和临床过程。
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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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