Genetic burden in neonatal and pediatric-onset pulmonary hypertension: A single-center retrospective study using exome sequencing in a Chinese population.

Objective: This single-center retrospective study aimed to investigate the genetic factors contributing to neonatal and pediatric pulmonary hypertension in a Chinese population using trio whole-exome sequencing (trio-WES).

Method: This retrospective analysis reviewed the clinical and genetic profiles of children under 18 years of age diagnosed with pulmonary hypertension between March 2017 and March 2022. The diagnosis of pediatric pulmonary hypertension was confirmed through echocardiography and catheterization. Trio-WES was performed on the patients and their parents after obtaining informed consent.

Results: A total of 51 children with neonatal and pediatric pulmonary hypertension were included, comprising 20 with pediatric pulmonary arterial hypertension and 31 with persistent pulmonary hypertension of the newborn. Trio-WES detected 16 pathogenic or likely pathogenic variants in 14 patients across ten genes, including: BMPR2 (n = 2), CHD7 (n = 2), FOXF1 (n = 2), MED13L (n = 1), TNNI3 (n = 2), ALMS1 (n = 1), KMT2D (n = 2), NKX2-1 (n = 1), NONO (n = 1), and CACNA1E (n = 1). In addition, two patients exhibited de novo pathogenic copy number variations.

Conclusion: Our findings demonstrate the significant diagnostic value of trio-WES in pediatric pulmonary hypertension, supporting its recommendation for these patients.