中文摘要：

高原肺水肿（high-altitude pulmonary edema, HAPE）是一种高原特发性疾病，其发病与遗传因素有一定关联。本研究对一个HAPE相关的家系展开遗传学调查，然后利用外显子组测序筛查了包括先证者在内的6名HAPE病史成员以及先证者的母亲共7个成员的遗传变异，结果发现18个HAPE相关的潜在遗传变异（9个SNVs和9个Indels）。利用SIFT，PolyPhen-2和PROVEAN等3种软件对这些遗传变异进行蛋白功能危害性分析，结果发现定位于CFHR4基因的SNV（p.L85F）以及定位于OXER1基因的SNV（p．R176C）具有高危害性，且OXER1的功能与HAPE低氧诱导通路存在高度关联，它们可作为该家系中HAPE相关的候选病理性变异。此外，还有部分SNVs（NMBp．S150P、APOBP．14194T和EIF4ENIFI p．Q763P）以及Indels（KCNJ12P．EE333—334E、ANKRD31p．LMN251-253LN和OR2A14p．HFFC175-178HFC），其遗传变异同样具有一定危害，可作为潜在的HAPE相关遗传变异。本研究首次通过外显子组测序直接筛选与一中国HAPE家系相关的遗传变异，为后续揭示HAPE发病机制提供了新线索。

英文摘要：

High-altitude pulmonary edema （HAPE） is one of idiopathic mountain sicknesses that occur in healthy lowlanders when they quickly ascend to altitudes exceeding 2500 m above sea levels within 1-7 days. Growing evidence suggests that genetics plays an important role in the risk of HAPE. In this study, we recruited a Chinese HAPE family and screened genetic variations in the 7 family members （including 6 family members with a medical history of HAPE and the propositus＇s mother） by whole-exome sequencing. The results showed 18 genetic variations （9 SNVs and 9 Indels） were related to HAPE. Two SNV sites （CFHR4 （p.L85F） and OXER1 （p.R176C）） were predicted to be damaging and alter protein functions by SIFT, PolyPhen-2 and PROVEAN software. The biological function of OXER1 was highly related to the hypoxia-inducible factor pathway. Therefore, those two sites were identified as can- didate pathological variations. Moreover, other SNVs （NMB p.S150P, APOB p.I4194T, EIF4ENIF1 p.Q763P） and Indels （KCNJI2 p.EE333-334E, ANKRD31 p.LMN251-253LN, OR2AI4 p.HFFC175-178HFC） were also predicted to be damaging as well, which also might be considered as potential candidate pathological variations related to HAPE. Collectively we firstly screened the susceptibility genes in a Chinese HAPE family by whole-exome se- quencing, which will provide new clues for further mechanistic studies of HAPE.