功能评估和表型的异质性SFTPA1和SFTPA2突变在间质性肺疾病和肺癌
- PMID:32855221
- DOI:10.1183/13993003.02806 -2020
功能评估和表型的异质性SFTPA1和SFTPA2突变在间质性肺疾病和肺癌
文摘
作品简介:间质性肺疾病(ILDs)可以由突变引起的SFTPA1和SFTPA2基因,其中编码复杂SP-A表面活性剂蛋白(SP)。只有11SFTPA1或SFTPA2突变到目前为止报道在世界范围内,其中5例已经功能评估。ILD框架的分子诊断,我们确定了14个独立患者致病SFTPA1或SFTPA2突变。本研究旨在功能评估确定的11种不同的突变,并准确描述疾病表型影响的病人和他们的亲属。
方法:11的后果SFTPA1或SFTPA2突变分析两在体外通过研究生产和相应的突变蛋白和分泌体外在肺组织样本,通过分析SP-A表达式。相关的疾病表型被记录。
结果:11确定突变的蛋白质生产保存但分泌被废除。肺SP-A可用六个病人的表达模式改变,家族病史报告ILD和/或肺腺癌14个家庭中就有13人(93%)。在28日SFTPA1或SFTPA2突变携带者,ILD发病的平均年龄是45岁(范围-65 - 0.6年)和48%接受肺移植(平均年龄51岁)。七个航空公司是无症状的。
讨论:这项研究,扩展了分子和SP-A障碍的临床表现,显示致病SFTPA1或SFTPA2突变的后果相似SP-A分泌细胞模型和肺组织免疫染色,而他们与高度可变的表型表达疾病有关,从严重的形式要求肺移植不完全外显率。
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利益冲突声明
利益冲突:m·勒让德没有披露。利益冲突:a .屁股没有披露。利益冲突:r . Borie报告赠款从勃林格殷格翰的发言和罗氏公司和个人费用,和个人费用从Savapharma外提交的工作。利益冲突:mp。r没有披露。利益冲突:d Bouvry没有披露。利益冲突:大肠Filhol-Blin没有披露。利益冲突:t Desroziers没有披露。利益冲突:诉nautica没有披露。利益冲突:b Copin没有披露。 Conflict of interest: F. Dastot Le Moal has nothing to disclose. Conflict of interest: M. Héry has nothing to disclose. Conflict of interest: P. Duquesnoy has nothing to disclose. Conflict of interest: N. Allou has nothing to disclose. Conflict of interest: A. Bergeron has nothing to disclose. Conflict of interest: J. Bermudez has nothing to disclose. Conflict of interest: A. Cazes has been invited to national and international meetings, and/or has received grants and/or personal fees for various activities from Boehringer Ingelheim and Roche, outside the submitted work. Conflict of interest: A-L. Chene has nothing to disclose. Conflict of interest: V. Cottin reports personal fees for lectures and advisory board work and non-financial support for meeting attendance from Actelion; grants, personal fees for lectures and advisory board work, and non-financial support for meeting attendance from Boehringer Ingelheim; personal fees for advisory board and data monitoring committee work from Bayer/MSD and Galapagos; personal fees for lectures and advisory board work from Novartis; personal fees for lectures, consultancy, data monitoring committee and steering committee work, and non-financial support for meeting attendance from Roche/Promedior; personal fees for lectures from Sanofi and AstraZeneca; personal fees for data monitoring committee work from Celgene and Galecto; and personal fees for advisory board work from Shionogi, outside the submitted work. Conflict of interest: B. Crestani has nothing to disclose. Conflict of interest: J-C. Dalphin has nothing to disclose. Conflict of interest: C. Dombret has nothing to disclose. Conflict of interest: B. Doray has nothing to disclose. Conflict of interest: C. Dupin reports personal fees for lectures and advisory board work, and non-financial support and meeting invitations from AstraZeneca; personal fees for lectures, non-financial support and meeting invitations from Boehringer and Novartis; personal fees for research and lectures, and non-financial support and meeting invitations from GSK; personal fees for lectures and meeting invitations from Chiesi; personal fees for lectures and advisory board work, and non-financial support from Sanofi; and personal fees, non-financial support and meeting invitations from Roche, outside the submitted work. Conflict of interest: V. Giraud has nothing to disclose. Conflict of interest: A. Gondouin has nothing to disclose. Conflict of interest: L. Gouya has nothing to disclose. Conflict of interest: D. Israël-Biet has nothing to disclose. Conflict of interest: C. Kannengiesser has nothing to disclose. Conflict of interest: A. Le Borgne has nothing to disclose. Conflict of interest: S. Leroy has nothing to disclose. Conflict of interest: E. Longchampt has nothing to disclose. Conflict of interest: G. Lorillon has nothing to disclose. Conflict of interest: H. Nunes has nothing to disclose. Conflict of interest: C. Picard has nothing to disclose. Conflict of interest: M. Reynaud-Gaubert has nothing to disclose. Conflict of interest: J. Traclet has nothing to disclose. Conflict of interest: P. de Vuyst has nothing to disclose. Conflict of interest: A. Coulomb L'Hermine has nothing to disclose. Conflict of interest: A. Clement has nothing to disclose. Conflict of interest: S. Amselem has nothing to disclose. Conflict of interest: N. Nathan reports a 2018 AstraZeneca Mobility Grant from Société de pneumologie pédiatrique et d'allergologie (France), outside the submitted work.
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小说在特发性肺纤维化罕见的遗传变异。欧元和j . 2020年12月24日,56 (6):2003252。doi: 10.1183/13993003.03252 -2020人。打印2020年12月。 欧元和j . 2020。 PMID:33361455 没有可用的抽象。
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