@Article{chd.2022.021626,
AUTHOR = {Rui Jiang, Kaisheng Lai, Jianping Xu, Xiang Feng, Shaoye Wang, Xiaojian Wang, Zhe Liu},
TITLE = {<i>NOTCH3</i> Mutations and CADASIL Phenotype in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease},
JOURNAL = {Structural and Congenital Heart Disease},
VOLUME = {17},
YEAR = {2022},
NUMBER = {6},
PAGES = {675--686},
URL = {http://www.techscience.com/schd/v17n6/50103},
ISSN = {3071-1738},
ABSTRACT = {<b>Background:</b> The etiology of pulmonary arterial hypertension associated with congenital heart disease (PAHCHD) is complicated and the phenotype is heterogeneous. Genetic defects of <i>NOTCH3</i> were associated with
cerebral disease and pulmonary hypertension. However, the relationship between <i>NOTCH3</i> mutations and the
clinical phenotype has not been reported in CHD-PAH. <b>Methods: </b>We eventually enrolled 142 PAH-CHD patients
from Fuwai Hospital. Whole exome sequencing (WES) was performed to screen the rare deleterious variants of
<i>NOTCH3</i> gene. <b>Results:</b> 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 <i>NOTCH3</i> were identified in five cases.
Patients 2, 5, 8 and 11 carried the same <i>NOTCH3</i> 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 <i>NOTCH3</i> 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. <b>Conclusions:</b> We first reported the <i>NOTCH3</i> rare mutations
and CADASIL phenotypes in CHD-PAH patients. The <i>NOTCH3</i> 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.},
DOI = {10.32604/chd.2022.021626}
}