シンポジウム10（I-S10）
小児の肺動脈性肺高血圧へのアプローチ：最近のエビデンス

[I-S10-03] 小児期発症肺動脈性肺高血圧症における遺伝子異常

^○千田 礼子 (陸上自衛隊 第9師団司令部)

Recently, some novel gene mutations causing pulmonary arterial hypertension (PAH) were identified. “Nice classification”, the latest classification of PAH, proposed 6 disease-causing genes of PAH; BMPR2, ALK1, ENG, SMAD8 (SMAD9 ), CAV1 and KCNK3. These genetic studies of PAH have considerably enhanced our understanding of the molecular mechanisms of PAH. However, clinical outcomes in each gene mutation carrier in PAH are still unclear. There are several studies referring to the relation between genotype and prognosis, but no report has investigated it in childhood PAH. We conducted a follow-up survey to clarify the clinical features and interrelations between gene mutations and outcomes in pediatric PAH. In our study, childhood PAH with BMPR2 mutation had the poorest outcome. ALK1 mutation carriers tended to have worse outcomes than mutation noncarriers. The study indicated that it is important to consider an aggressive treatment for BMPR2 or ALK1 mutation carriers.
About 30% of familial PAH cases and 60–90% of sporadic PAH cases have no mutations in BMPR2, ALK1, ENG, SMAD8 (SMAD9 ), CAV1 or KCNK3. We here review the progress of research on other disease-causing candidate genes of PAH, including BMPR1B (ALK6 ) and NOTCH3, which we have identified recently.