Abstract 15793: Role of X Gene Variant in Childhood Pulmonary Arterial Hypertension

Background: Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, the majority of PAH cases have no disease-causing variants in these genes. Methods: In order to find disease-causing variants, we performed direct sequencing and multiplex ligation-dependent probe amplification to analyze 16 families with multiple affected family members with PAH. In one of the 16 families with PAH, there were no disease-causing variants in BMPR2, ACVRL1, ENG, SMAD1/4/8, BMPR1B, NOTCH3, CAV1, or KCNK3. In this family, a female proband and her paternal aunt developed PAH in their childhood. To identify novel disease-causing variants efficiently, whole-exome next-generation sequencing was performed in the 2 PAH patients and the proband’s healthy mother. Based on the result, we performed functional analysis using human pulmonary arterial smooth muscle cells (hPASMCs), candidate gene siRNA, and candidate gene constructs. We analyzed inflammatory cascade and p5...