Department of Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Comput Biol Chem. 2022 Jun;98:107665. doi: 10.1016/j.compbiolchem.2022.107665. Epub 2022 Mar 12.
Till now not many studies have been conducted to classify PAH gene variants according to American College of Medical Genetics and Genomics (ACMG-AMP) guidelines. The aim of this study was to collect all PAH gene variants reported among Iranian population and investigate their pathogenicity based on ACMG-AMP guidelines. Systematic collection of PAH gene variants, verification of variants, in silico analysis, and application of ACMG-AMP guidelines were the main steps in performing the present study. A total of 267 unique variants were identified; according to ACMG-AMP guidelines, 90, 40, 71, 14, and 52 variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), and benign (B), respectively. The need to pay more attention to synonymous and missense variants with low or no impact on protein function as well as intronic variants, whether they are deep or are close to intron/exon boundaries, was a highlight of this study. Due to the fact that few functional studies are performed on these variants, it is suggested that they be analyzed first using bioinformatics tools, and if positive results are obtained, then functional studies can be designed.
到目前为止，根据美国医学遗传学与基因组学学院（ACMG-AMP）指南，对肺动脉高压（PAH）基因变异进行分类的研究并不多。本研究的目的是收集所有在伊朗人群中报道的 PAH 基因变异，并根据 ACMG-AMP 指南调查其致病性。系统收集 PAH 基因变异、变异验证、计算机分析以及应用 ACMG-AMP 指南是进行本研究的主要步骤。共鉴定出 267 个独特的变异；根据 ACMG-AMP 指南，90、40、71、14 和 52 个变异分别被归类为致病性（P）、可能致病性（LP）、意义不明的变异（VUS）、可能良性（LB）和良性（B）。本研究的一个重点是需要更加关注对蛋白质功能影响低或无影响的同义变异和错义变异，以及无论它们是深还是靠近内含子/外显子边界的内含子变异。由于对这些变异进行的功能研究较少，因此建议首先使用生物信息学工具进行分析，如果得到阳性结果，则可以设计功能研究。
