机构：[1]Shanghai Key Laboratory of Birth Defects, National Health Commision (NHC)Key Laboratory of Neonatal Diseases, Division of Neonatology, NationalCenter for Children’s Health, Children’s Hospital of Fudan University,Shanghai 201102, China[2]Xiamen Key Laboratory of Neonatal Diseases,Neonatal Medical Center, Xiamen Children’s Hospital, Children’s Hospital ofFudan University (Xiamen Branch), Xiamen 361006, Fujian, China[3]Division ofPulmonology, Children’s Hospital of Fudan University, Shanghai 201102, China[4]Zhuhai Maternal and Children’s Hospital, Zhuhai 519001, Guangdong, China[5]Department of Population and Quantitative Health Sciences, University ofMassachusetts Medical School, Worcester, MA 01655, USA[6]Imunobio, Shenzhen,Guangdong, China[7]Division of Neonatology, Children’s Hospital of FudanUniversity, Shanghai 201102, China[8]Key Laboratory of Birth Defects, Children’sHospital of Fudan University, Shanghai 200436, China
Persistent pulmonary hypertension of the newborn (PPHN) is characterized by sustained high levels of pulmonary vascular resistance after birth with etiology unclear; Arterial blood oxygen saturation of Tibetan newborns at high latitudes is higher than that of Han newborns at low latitudes, suggesting that genetic adaptation may allow sufficient oxygen to confer Tibetan populations with resistance to pulmonary hypertension; We have previously identified genetic factors related to PPHN through candidate gene sequencing; In this study, we first performed whole exome sequencing in PPHN patients to screen for genetic-related factors.
In this two-phase genetic study, we first sequenced the whole exome of 20 Tibetan PPHN patients and compared it with the published genome sequences of 50 healthy high-altitude Tibetanshypoxia-related genes, a total of 166 PPHN-related variants were found, of which 49% were from 43 hypoxia-related genes; considering many studies have shown that the differences in the genetic background between Tibet and Han are characterized by hypoxia-related genetic polymorphisms, so it is necessary to further verify whether the association between hypoxia-related variants and PPHN is independent of high-altitude life. During the validation phase, 237 hypoxia-related genes were sequenced in another 80 Han PPHN patients living in low altitude areas, including genes at the discovery stage and known hypoxia tolerance, of which 413 variants from 127 of these genes were shown to be significantly associated with PPHN.hypoxia-related genes.
Our results indicates that the association of hypoxia-related genes with PPHN does not depend on high-altitude life, at the same time, 21 rare mutations associated with PPHN were also found, including three rare variants of the tubulin tyrosine ligase-like family member 3 gene (TTLL3:p.E317K, TTLL3:p.P777S) and the integrin subunit alpha M gene (ITGAM:p.E1071D). These novel findings provide important information on the genetic basis of PPHN.
基金：
This project was supported by National Natural Science Foundation of China
(Program No. 81701351, No. 81701498 and No.81720108018), Shanghai
Municipal Commission of Health and Family Planning (GDEK201701), by
Shanghai Municipal Science and Technology Major Project (2018SHZDZX05),
and by Super Postdoctoral Program of Fudan University.
第一作者机构：[1]Shanghai Key Laboratory of Birth Defects, National Health Commision (NHC)Key Laboratory of Neonatal Diseases, Division of Neonatology, NationalCenter for Children’s Health, Children’s Hospital of Fudan University,Shanghai 201102, China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Key Laboratory of Birth Defects, National Health Commision (NHC)Key Laboratory of Neonatal Diseases, Division of Neonatology, NationalCenter for Children’s Health, Children’s Hospital of Fudan University,Shanghai 201102, China[4]Zhuhai Maternal and Children’s Hospital, Zhuhai 519001, Guangdong, China
推荐引用方式(GB/T 7714)：
Mingbang Wang,Deyi Zhuang,Mei Mei,et al.Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn.[J].RESPIRATORY RESEARCH.2020,21(1):53.doi:10.1186/s12931-020-1314-5.
APA：
Mingbang Wang,Deyi Zhuang,Mei Mei,Haiyan Ma,Zixiu Li...&Wenhao Zhou.(2020).Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn..RESPIRATORY RESEARCH,21,(1)
MLA：
Mingbang Wang,et al."Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn.".RESPIRATORY RESEARCH 21..1(2020):53
