Identification of a novel missense variant in SPDL1 associated with idiopathic pulmonary fibrosis
Identification of a novel missense variant in SPDL1 associated with idiopathic pulmonary fibrosis
复制标题
鉴定与特发性肺纤维化相关的 SPDL1 中的新型错义变异
DOI：
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
S. Petrovski
中科院分区：
文献类型：
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作者：
R. Dhindsa;J. Mattsson;A. Nag;Quanli Wang;L. Wain;R. Allen;E. Wigmore;K. Ibáñez;D. Vitsios;Sri V. V. Deevi;Sebastian Wasilewski;M. Karlsson;G. Lassi;H. Olsson;D. Muthas;A. Mackay;L. Murray;S. Young;C. Haefliger;T. Maher;M. Belvisi;G. Jenkins;P. Molyneaux;A. Platt;S. Petrovski
特发性肺纤维化（IPF）是一种以进行性、破坏性肺瘢痕为特征的致命疾病。尽管取得了重大进展，但该病的遗传决定因素仍未完全确定。利用来自752例散发性IPF患者和119,055例对照的下一代测序数据，我们进行了变异和基因水平分析，以确定新的IPF遗传风险因素。我们的变异水平分析揭示了SPDL1中一个新的罕见错义变异（NM_017785.5 p.a g20gln; p = 2.4 × 10−7，优势比= 2.87）。该信号在FinnGen队列中被独立复制（组合p = 2.2 × 10−20），牢固地将该变异与新的IPF风险等位基因联系起来。SPDL1编码Spindly，这是一种在细胞分裂过程中参与有丝分裂检查点信号传导的蛋白质，以前未在纤维化中描述过。我们的研究结果强调了IPF的新机制，为一种巨大的未满足需求的疾病提供了新的治疗发现的潜力。
Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite significant progress, the genetic determinants of this disease remain incompletely defined. Using next generation sequencing data from 752 individuals with sporadic IPF and 119,055 controls, we performed both variant- and gene-level analyses to identify novel IPF genetic risk factors. Our variant-level analysis revealed a novel rare missense variant in SPDL1 (NM_017785.5 p.Arg20Gln; p = 2.4 × 10−7, odds ratio = 2.87). This signal was independently replicated in the FinnGen cohort (combined p = 2.2 × 10−20), firmly associating this variant as a novel IPF risk allele. SPDL1 encodes Spindly, a protein involved in mitotic checkpoint signalling during cell division that has not been previously described in fibrosis. Our results highlight a novel mechanism underlying IPF, providing the potential for new therapeutic discoveries in a disease of great unmet need.
DOI：
10.1164/rccm.201308-1483st
发表时间：
2013-09-15
影响因子：
24.7
作者：
Travis, William D.;Costabel, Ulrich;Valeyre, Dominique
通讯作者：
Valeyre, Dominique
分析特发性肺纤维化患者中端粒酶基因中蛋白质改变的变体及其与MUC5B共同变异状态的关联：候选基因测序研究。
DOI：
10.1016/s2213-2600(18)30135-8
发表时间：
2018-08
期刊：
The Lancet. Respiratory medicine
影响因子：
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作者：
Dressen A;Abbas AR;Cabanski C;Reeder J;Ramalingam TR;Neighbors M;Bhangale TR;Brauer MJ;Hunkapiller J;Reeder J;Mukhyala K;Cuenco K;Tom J;Cowgill A;Vogel J;Forrest WF;Collard HR;Wolters PJ;Kropski JA;Lancaster LH;Blackwell TS;Arron JR;Yaspan BL
通讯作者：
Yaspan BL