Variants in Japanese Patients With Pulmonary Arterial Hypertension

Recent studies have illuminated the importance of tet-methylcytosine-dioxygenase-2 () in pulmonary arterial hypertension (PAH). We aimed to clarify the frequency of variants in Japanese PAH patients. Among whole-exome sequencing of 145 Japanese patients with idiopathic or heritable PAH, 3 patients (2.1%) had a germline heterozygous missense variant in (c.3116C > T, p.Ser1039Leu). The allele frequency is 0.15% in the gnomAD database, and 0.2% among 3554 in the general Japanese population. These 3 patients needed combination therapy including continuous prostacyclin infusion. Our study identified a novel variant, and may have effects on the onset and/or disease progression of PAH.