Table 1.
Variants Identified in Childhood-Onset Pulmonary Arterial Hypertension.
| Patient | Sex | Age of Onset | Diagnosis | Variant Identified | Mutation Category | GnomAD MAF | Variant Identifier(s) | CADD Score | SIFT Score | PolyPhen2 (HumVar) | Mutation Taster |
|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | M | 9 y | APAH–CHD (ASD) |
ATP13A3 (exon 11) NM_024524.4 c.1148C>A (p.Thr383Lys) |
Missense * | - | Novel | 32 | 0.001, D | 0.991, D | 1.0, D |
| P2 | F | 3 y | IPAH |
BMP10 (exon 1) NM_014482.3 c.247G>A (p.Glu83Lys) |
Missense | 0.000009 | dbSNP: rs1192957334; Not in ClinVar |
28 | 0.047, D | 0.999, D | 1.0, D |
| P3 | F | <5 y | IPAH |
PDGFD (exon 4) NM_025208.5 c.550G>A (p.Glu184Lys) |
Missense | - | dbSNP: rs769639743; Not in ClinVar |
28.2 | 0.007, D | 0.980, D | 0.9998, D |
| P4 | M | 19 m | IPAH |
ABCC8 (exon 7) NM_000352.6 c.1069G>A (p.Val357Ile) |
Missense | 0.000018 | dbSNP: rs771392416; Not in ClinVar |
23 | 0.235, T | 0.042, B | 1.0, D |
| P5 | F | 4.5 y | HPAH (mother also affected) |
SMAD9 (exon 6) NM_001127217.3 c.1117G>A (p.Val373Ile) |
Missense | 0.00013 | dbSNP: rs140504903; ClinVar: VCV000311894 |
27 | 0.001, D | 0.936, D | 1.0, D |
APAH–CHD: PAH associated with congenital heart disease; ASD: atrial septal defect; B: benign; CADD: Combined Annotation Dependent Depletion; D: damaging (SIFT), probably damaging (PolyPhen2) or disease causing (Mutation Taster); IPAH: idiopathic pulmonary arterial hypertension; HPAH: heritable pulmonary arterial hypertension; MAF: minor allele frequency in gnomAD v2.1.1 (controls); m: months; SIFT: Sorting Independent from Tolerant; T: tolerated; y: years. * The ATP13A3 missense variant in Patient 1 is located within the consensus splice region.