c.226G>A (p.Gly76Ser) as a Novel Causative Mutation for Pulmonary Arterial Hypertension.

Background Recently, some studies reported the pulmonary artery hypertension (PAH)-associated genes. However, a majority of patients with familial or sporadic PAH lack variants in the known pathogenic genes. In this study, we investigated the new causative gene variants associated with PAH. Methods and Results Whole-exome sequencing in 242 Japanese patients with familial or sporadic PAH identified a heterozygous substitution change involving c.226G>A (p.Gly76Ser) in tumor necrotic factor receptor superfamily 13B gene () in 6 (2.5%) patients. controls the differentiation of B cell and secretion of inflammatory cytokines and may be involved in vascular inflammation. In silico structural analysis simulation demonstrated the structural instability of the N-terminal region of the protein synthesized from p.Gly76Ser variant. These suggest that the p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels. Conclusions p.Gly76Ser variant is a candidate of novel causative gene variant for PAH.