ABSTRACT
Objectives: To investigate the genetic mutation in a Chinese family with Pulmonary Arterial Hypertension (PAH). Methods: Whole exome sequencing was performed in two patients and two healthy family members in the PAH pedigree. Patient-specific variations were screened by bioinformatics methods and compared between groups. To further identify the association between these variations and PAH, Sanger sequencing was used to analyze the genotype of PAH patients and 100 healthy controls. Results: Two affected persons were found among the eight family members. The patients was presented as dyspnea after exercise, and right-heart catheterization was performed to measure the mean pulmonary arterial pressure (mPAP, 77 mmHg), cardiac output (CO, 4.92 L/min), and pulmonary vascular resistance (PVR, 13.4 Wood units). The hereditary characteristic in this family presented in mother and child, suggesting an autosomal dominant patter. Exome sequencing, mutation detection and sanger variants validation revealed a novel heterozygous frameshift mutation (c.747_748 insCCTTTGATGGAACATGA:p.V250fs) in the BMPR2 gene. Meanwhile, this heterozygous insertion mutation was absent in 100 ethnically matched control samples screened by direct sanger sequencing. Conclusions: Our study revealed a novel heterozygous frameshift mutation in the BMPR2 gene, expanding the BMPR2 mutation spectrums.