Service de Pneumologie A Hôpital Bichat, APHP, Paris, France, Université Paris Cité, Inserm, PHERE, Université Paris Cité.
Laboratoire de Génétique, Hôpital Bichat.
Curr Opin Pulm Med. 2024 Sep 1;30(5):473-483. doi: 10.1097/MCP.0000000000001088. Epub 2024 Jun 19.
The identification of extra-pulmonary symptoms plays a crucial role in diagnosing interstitial lung disease (ILD). These symptoms not only indicate autoimmune diseases but also hint at potential genetic disorders, suggesting a potential overlap between genetic and autoimmune origins.
Genetic factors contributing to ILD are predominantly associated with telomere (TRG) and surfactant-related genes. While surfactant-related gene mutations typically manifest with pulmonary involvement alone, TRG mutations were initially linked to syndromic forms of pulmonary fibrosis, known as telomeropathies, which may involve hematological and hepatic manifestations with variable penetrance. Recognizing extra-pulmonary signs indicative of telomeropathy should prompt the analysis of TRG mutations, the most common genetic cause of familial pulmonary fibrosis. Additionally, various genetic diseases causing ILD, such as alveolar proteinosis, alveolar hemorrhage, or unclassifiable pulmonary fibrosis, often present as part of syndromes that include hepatic, hematological, or skin disorders.
This review explores the main genetic conditions identified over the past two decades.
肺外症状的识别对间质性肺疾病（ILD）的诊断起着至关重要的作用。这些症状不仅表明自身免疫性疾病，还提示潜在的遗传疾病，表明遗传和自身免疫起源之间存在潜在的重叠。
与 ILD 相关的遗传因素主要与端粒（TRG）和表面活性剂相关基因有关。虽然表面活性剂相关基因的突变通常仅表现为肺部受累，但 TRG 突变最初与称为端粒体病的综合征性肺纤维化形式有关，其可能具有不同外显率的血液学和肝脏表现。识别提示端粒体病的肺外征象应促使分析 TRG 突变，这是家族性肺纤维化最常见的遗传原因。此外，导致间质性肺病的各种遗传疾病，如肺泡蛋白沉积症、肺泡出血或无法分类的肺纤维化，通常作为包括肝脏、血液或皮肤疾病在内的综合征的一部分出现。
本综述探讨了过去二十年中确定的主要遗传疾病。
