Open Access iconOpen Access


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

Rui Jiang1,3,*, Kaisheng Lai2, Jianping Xu1, Xiang Feng1, Shaoye Wang1, Xiaojian Wang3, Zhe Liu2

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

* Corresponding Author: Rui Jiang. Email: email

Congenital Heart Disease 2022, 17(6), 675-686.


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 with cerebral disease and pulmonary hypertension. However, the relationship between NOTCH3 mutations and the clinical phenotype has not been reported in CHD-PAH. Methods: We eventually enrolled 142 PAH-CHD patients from Fuwai Hospital. Whole exome sequencing (WES) was performed to screen the rare deleterious variants of NOTCH3 gene. Results: This PAH-CHD cohort included 43 (30.3%) men and 99 (69.7%) women with the mean age 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-spot mutation 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 associated with 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 mutations and CADASIL phenotypes in CHD-PAH patients. The NOTCH3 rare variants were with a relatively high positive rate and CADASIL phenotypes were likely enriched in PAH-CHD patients. The preoperative neurological examination might be recommended for PAH-CHD patients to determine the surgical contraindications and reduce intraoperative neurological complications.


Cite This Article

Jiang, R., Lai, K., Xu, J., Feng, X., Wang, S. et al. (2022). NOTCH3 Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease. Congenital Heart Disease, 17(6), 675–686.

cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 1287


  • 539


  • 1


Share Link