Center for Pulmonary Hypertension, Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital, Heidelberg, Germany.
Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Eur Respir J. 2023 Feb 23;61(2). doi: 10.1183/13993003.01471-2022. Print 2023 Feb.
Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.
肺动脉高压（PAH）是一种罕见疾病，可能由（可能）致病性种系基因组变异引起。除了最常见的疾病基因（骨形态发生蛋白受体 2）外，现在已知还有几个基因，有些属于不同的功能类别，也容易导致 PAH 的发生。因此，专科和非专科临床医生和医疗保健专业人员越来越多地面临一系列关于 PAH 患者和/或相关家庭成员是否需要进行基因检测、检测方法以及检测的获益/风险的问题。我们提供了一种基于共识的方法，用于推荐基因咨询以及评估当前疾病基因检测的最佳实践。我们提供了一个框架和在遗传咨询过程中向患者和亲属提供的信息类型，并描述了目前已知的要进行分析的疾病因果基因。在 PAH 患者的管理方案中纳入分子遗传学检测的益处包括：识别通过其他诊断方法分类错误的个体；优化表型特征以聚集结果数据，包括临床试验，以及通过级联筛查重要地检测到健康的因果变异携带者，应为其提供定期评估。
