Table 2.
Evaluated Genes | Number of Patients | PH Groups (IPAH, HPAH, PVOD, CHD, Others) | Diagnostic Yield of Genetic Analysis * | Results in IPAH/HPAH | Results in PVOD | Results in CHD-PAH | Age at Diagnosis of Mutation Carriers (Mean) | |
---|---|---|---|---|---|---|---|---|
Chida et al., 2012 [18] | BMPR2, ACVRL1, SMAD8, BMPR1B | 57 | 46/10/0/0/0 | 25/54 (46.3%) | BMPR2 n = 13/57 (33%) ALK1 n = 6/57 (13%) SMAD8 n = 1/57 (1.7%) BMPR1B n = 2 (3.5%) |
NA | NA | 9.2 |
Levy et al., 2016 [19] | BMPR2, ACVRL1, TBX4, KCNK3, EIF2AK4 | 42 | 35/5/3/23 | 14/42 (33.3%) | BMPR2 n = 5/40 (12.5%) ACVRL1 n = 4/40 (10%) TBX4 n = 3/40 (7.5%) |
EIF2AK4 2/3 (67.7%) | 0/23 (0%) | 8.3 |
Zhu et al., 2018 [9] | BMPR2, TBX4, ACVRL1, BMPR1B, CAV1, EIF2AK4, ENG, KCNK3, SMAD4, SMAD9 | 155 | 130/25 | 48/155 (31.0%) | BMPR2 n = 27/155 (17.7%) TBX4 n = 12/155 (7.4%) ACVRL1 n = 3/155 (1.9%), KCNK3 n = 2/155 (1.3%), SMAD9 n = 1/155 (0.6%) |
N/A | N/A | |
Haarman et al., 2020 [20] | BMPR2, ACVRL1, CAV1, ENG, KCNK3, SMAD9, TBX4, EIF2AK4, VHL, MMACHC, CBLC, ACTA2 | 70 | 19/16/5/20/10 | 19/70 (27.1%) | BMPR2 n = 7/35 (20%) TBX4 n = 7/35 (20%) ACVRL1 n = 1/35 (2.8%), PTPN11 n = 2/35 (5.7%) KCNK3 n = 1/35 (2.8%) |
EIF2AK4 2/5 (40.0%) | ACTA2 1/20 (5%) | 2.8 years TBX4 and14.0 years in BMPR2 carriers |
PPHNet Registry. 2021 [6] | BMPR2, ACVRL1, SMAD9, CAV1, KCNK3, TBX4, GDF2 | 40 FPAH |
0/40/0/0/0 | 36/40 heritable cases (90.0%) ** | BMPR2 n = 17/40 (43%) TBX4 n = 6/40 (15%) ALK/ENG n = 5/40 (5%) GDF2 n = 2 /40 (5%) CAV1 n = 1/40 (3%) KCNK3 n = 1 (3%) |
N/A | N/A | N/A |
REHIPED registry (this study) | ABCC8, ACVRL1, BMPR1B, BMPR2, CAV1, CBLN2, CPS1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, MMACHC, NOTCH3, SARS2, SMAD1, SMAD4, SMAD5, SMAD9, TBX4, and TOPBP1 | 98 | 28/18/8/28/16 | 44/98 (44.9%) | BMPR2 n = 12/50 (24.0%) TBX4 n = 4/50 (8.0%) KCNK3 n = 2/50 (4.0%) ACVRL1 n = 1 (2.0%) BMPR1B n = 1 (2.0%) GDF2 n = 1 (2.0%) |
EIF2AK4N = 8/8 (100.0%) | N = 7/28 (25.0%) - BMPR2 n = 3 - ENG n = 1 - CPS1 n = 1 - ABCC8/SMAD1 n = 1 - SOX17 n = 1 |
8.0 |