TY - T1的功能评估和表型异质性的< em > SFTPA1 < / em >和< em > SFTPA2 < / em >突变在间质性肺疾病和肺癌JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02806 -2020欧元六世- 56 - 6 SP - 2002806 AU -勒让德,玛丽盟——屁股,Afifaa盟——Borie拉斐尔AU - r,显示非盟- Bouvry,黛安娜AU - Filhol-Blin,艾米莉盟——Desroziers Tifenn AU - nautica,瓦莱丽盟——Copin布鲁诺AU - Dastot-Le Moal,佛罗伦萨AU -亨利,梅勒妮盟——Duquesnoy Philippe AU - Allou娜塔莉盟——Bergeron安妮AU -贝穆德斯,朱利安盟——caz Aurelie AU - Chene Anne-Laure盟——Cottin文森特AU -,伽马安基丁酸布鲁诺盟——Dalphin租用非盟- Dombret鳌,Doray贝蕾妮斯盟-杜宾,Clairelyne盟——Giraud Violaine盟——Gondouin安妮盟——Gouya Laurent AU - Israel-Biet,多米尼克•AU - Kannengiesser卡罗琳AU - Le Borgne Aurelie AU -勒罗伊,西尔维盟——Longchampt伊丽莎白盟——Lorillon Gwenael AU - Nunes,希拉里奥盟-皮卡德,Clément AU - Reynaud-Gaubert, Martine AU - Traclet, Julie AU - de Vuyst, Paul AU - Coulomb L'Hermine, Aurore AU - Clement, Annick AU - Amselem, Serge AU - Nathan，间质性肺疾病(ILDs)可由编码表面活性剂蛋白(SP)复合物SP- a的SFTPA1和SFTPA2基因突变引起。迄今为止，世界范围内仅报道了11例SFTPA1或SFTPA2突变，其中5例进行了功能评估。在ILD分子诊断框架下，我们鉴定了14例具有致病性SFTPA1或SFTPA2突变的独立患者。本研究旨在对11种不同的突变进行功能评估，并准确描述患者及其患病亲属的疾病表型。方法对11例SFTPA1或SFTPA2突变的结果进行体外分析，通过研究相应突变蛋白的产生和分泌，以及体外分析肺组织样本中SP-A的表达。记录了相关的疾病表型。Results For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6–65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic.Discussion This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.SFTPA1 and SFTPA2 mutations lead to similar alterations in SP-A secretion and lung tissue expression. They are associated with a highly variable phenotypic expression ranging from incomplete penetrance to severe interstitial lung diseases and lung cancer. https://bit.ly/30SrEVb ER -