Dept of Pulmonology, St Antonius ILD Center of Excellence, St Antonius Hospital, Nieuwegein, The Netherlands.
Division of Hearts and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
Eur Respir Rev. 2021 Feb 16;30(159). doi: 10.1183/16000617.0085-2020. Print 2021 Mar 31.
Genes involved in the production of pulmonary surfactant are crucial for the development and maintenance of healthy lungs. Germline mutations in surfactant-related genes cause a spectrum of severe monogenic pulmonary diseases in patients of all ages. The majority of affected patients present at a very young age, however, a considerable portion of patients have adult-onset disease. Mutations in surfactant-related genes are present in up to 8% of adult patients with familial interstitial lung disease (ILD) and associate with the development of pulmonary fibrosis and lung cancer.High disease penetrance and variable expressivity underscore the potential value of genetic analysis for diagnostic purposes. However, scarce genotype-phenotype correlations and insufficient knowledge of mutation-specific pathogenic processes hamper the development of mutation-specific treatment options.This article describes the genetic origin of surfactant-related lung disease and presents spectra for gene, age, sex and pulmonary phenotype of adult carriers of germline mutations in surfactant-related genes.
与肺表面活性剂生产相关的基因对于健康肺的发育和维持至关重要。表面活性剂相关基因的种系突变会导致各年龄段患者出现一系列严重的单基因肺疾病。大多数受影响的患者在很小的时候就出现症状，然而，相当一部分患者的疾病在成年后才出现。在高达 8%的家族性间质性肺疾病 (ILD) 的成年患者中存在表面活性剂相关基因的突变，并与肺纤维化和肺癌的发展相关。高疾病外显率和可变表达性突出了遗传分析在诊断目的方面的潜在价值。然而，基因型-表型相关性稀少，以及对突变特异性致病过程的了解不足，阻碍了针对特定突变的治疗方法的发展。本文描述了与肺表面活性剂相关的肺疾病的遗传起源，并介绍了表面活性剂相关基因的种系突变的成年携带者的基因、年龄、性别和肺表型谱。
