We studied a family in which multiple members had pulmonary arterial hypertension without identifiable mutations in any of the genes known to be associated with the disease, including BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole-exome sequencing. Additional patients with familial or idiopathic pulmonary arterial hypertension were screened for the mutations in the gene that was identified on whole-exome sequencing. All variants were expressed in COS-7 cells, and channel function was studied by means of patch-clamp analysis.
家族内に複数の肺動脈性肺高血圧症（PAH）患者がおり、この疾患との関連が認められている既知の遺伝子、BMPR2、ALK1、ENG、SMAD9、CAV1 などに変異が認められない１家族の調査を行った。家族のうち３人の全エクソーム塩基配列決定を行った。さらに別の家族性または特発性肺動脈性肺高血圧症の患者に対し、全エクソーム塩基配列決定で確認された遺伝子変異についてスクリーニングを行った。すべての多様体を COS-7 細胞で発現させ、チャネル機能をパッチクランプ法で解析した。
