NOTCH3 Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease  

作　　者：Rui Jiang Kaisheng Lai Jianping Xu Xiang Feng Shaoye Wang Xiaojian Wang Zhe Liu 

机构地区：[1]Department of Adult Cardiac Surgery,National Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing,China [2]BestNovo(Beijing)Medical Laboratory,Beijing,China [3]Key Laboratory of Pulmonary Vascular Medicine,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China

出　　处：《Congenital Heart Disease》2022年第6期675-686,共12页先天性心脏病（英文）

基　　金：Grant 81425002 from the National Science Fund for Distinguished Young Scholars;Grants 81670052,and 81870050 from the National Natural Science Foundation of China;Grant 2018ZX09711001-003-012 from the Drug Innovation Major Project,CAMS Fund for Key Laboratory of Pulmonary Vascular Medicine(2017PT32016).

摘　　要：Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.

关 键 词：Pulmonary arterial hypertension Congenital heart disease NOTCH3 Cerebral autosomal dominant arteriopathy with subcortical infarcts and lesions(CADASIL) 

分 类 号：R541[医药卫生—心血管疾病]