TY - T1的家族性肺动脉高血压由< em > KDR < / em >杂合的损失函数JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02165 -2019欧元SP - 1902165 AU -巢窝,梅勒妮盟——Montani大卫AU - Girerd,芭芭拉盟——Favrolt尼古拉斯AU - Riou,玛丽安非盟-副检察官,劳伦斯盟——Manaud格雷戈勒盟——Perros Frederic盟——伯爵,Stefan盟——莫雷尔,尼古拉斯·w . AU -亨伯特,马克•AU - Soubrier【摘要】近十年来，除了主要基因BMPR2外，还发现了几个导致多环芳烃的新基因。最近，在一项大型基因关联研究中发现了KDR基因参与的初步证据。方法我们对311例多环芳烃患者进行前瞻性的KDR基因分析，这些患者被转到临床分子实验室进行多环芳烃基因诊断。结果两例来自不同家系的重度多环芳烃患者的KDR基因发生功能缺失突变。这两个指标病例的临床特征是一氧化碳弥散能力低，血红蛋白调节(DLCOc)和肺间质病变。在一个家族中，分离分析显示，变异携带者要么表现出多环芳烃与低DLCOc相关，要么只表现出DLCOc下降，而非携带者的亲属则表现出正常的DLCOc。在第二个家庭中，只有一名受感染的携带者存活。他的母亲没有受到正常DLCOc的影响。结论通过描述两个家系中多环芳烃与KDR突变的分离，为KDR作为新鉴定的PAH致病基因提供了遗传学证据。在我们的研究中，KDR突变与以低DLCOc为特征的一种特殊形式的多环芳烃有关，并与肺实质疾病(包括间质性肺疾病和肺气肿)的放射学证据有关。该手稿最近已被《欧洲呼吸杂志》接受发表。 It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. EYRIES has nothing to disclose.Conflict of interest: Dr. MONTANI reports grants and personal fees from Actelion, grants and personal fees from Bayer, personal fees from GSK, personal fees from Pfizer, personal fees from MSD, outside the submitted work.Conflict of interest: Dr. GIRERD has nothing to disclose.Conflict of interest: Dr. FAVROLT has nothing to disclose.Conflict of interest: Dr. Riou has nothing to disclose.Conflict of interest: Dr. FAIVRE has nothing to disclose.Conflict of interest: Dr. Manaud has nothing to disclose.Conflict of interest: Dr. Perros has nothing to disclose.Conflict of interest: Dr. Gräf has nothing to disclose.Conflict of interest: Dr. Morrell reports personal fees from Morphogen-IX, outside the submitted work.Conflict of interest: Dr. Humbert reports personal fees from Acceleron, personal fees from Actelion, grants and personal fees from Bayer, grants and personal fees from GSK, personal fees from Merck, personal fees from United Therapeutics, outside the submitted work.Conflict of interest: Dr. SOUBRIER has nothing to disclose. ER -