Table 2.
High-throughput NGS studies investigating CHH patients
| Quaynor et al. (2016) | Wang et al. (2017) | Aoyama et al. (2017) | Cassatella et al. (2018) | Zhou et al. (2018) | Kim et al., (2019) | Amato et al. (2019 | Current study | ||
|---|---|---|---|---|---|---|---|---|---|
| Nr of CHH patients | 48 | 51 | 22 | 116 CHH | 72 CDGP | 153 | 28 | 130 | 38 |
| Nr of genes investigated | 261 | 164 | 27 | 25 | 83 | 69 | 36 | 41 | |
| Nr of patients with identified variant | NA | 26 (51%) | 12 (54.5%) | 59 (51%) | 5 (7%) | 87 (56%) | 11 (39%) | 43 (33%) | 22 (57%) |
| Ratio of cases with di-/oligogenic background | 19% | 9.8% | 0% | 15% | 1.4% | 19% | not reported | 6.9% | 21% |
| Genes with variants identified (frequency of detection in the partciular cohort) | AXL (6.3%) | PROKR2 (17.6%) | CHD7 (18.2%) | FGFR1 (15.5%) | AXL (1.4%) | RELN (20.3%) | FGFR1 (14.3%) | CHD7 (10.8%) | FGFR1 (12.5%) |
| FGFR1 (6.3%) | FGFR1 (13.7%) | ANOS1 (18.2%) | CHD7 (13.8%) | FGFR1 (1.4%) | PROKR2 (17.6%) | CHD7 (7.1%) | FGFR1 (8.5%) | GLI3 (7.5%) | |
| GLI3 (4.2%) | CHD7 (7.8%) | FGFR1 (13.6%) | PROKR2 (5.2%) | HS6ST1 (1.4%) | CHD7 (9.8%) | TACR3 (7.1%) | IGSF10 (5.4%) | NOTCH1 (7.5%) | |
| AMN1 (2.1%) | IL17RD (5.9%) | TACR3 (4.5%) | SOX10 (4.3%) | PROKR2 (1.4%) | ANOS1 (7.2%) | PROKR2 (3.6%) | GNRHR (5.4%) | MASTL (7.5%) | |
| CCKBR (2.1%) | ANOS1 (5.9%) | AXL (3.4%) | TAC3 (1.4%) | ERBB4 (6.5%) | ANOS1 (3.6%) | WDR11 (4.6%) | PROKR2 (5%) | ||
| CRY1 (2.1%) | FGF17 (2%) | GNRHR (3.4%) | FEZF1 (1.4%) | FGFR1 (6.5%) | SOX3 (3.6%) | ANOS1 (4.6%) | AMH (5%) | ||
| CXCR4 (2.1%) | KISS1R (2%) | SEMA3A (2.6%) | EGFR (5.9%) | TACR3 (3.8%) | JAG1 (5%) | ||||
| FGF13 (2.1%) | PROK2 (2%) | IL17RD (2.6%) | LHB (5.9%) | PROK2 (3.8%) | IL17RD (5%) | ||||
| GAP43 (2.1%) | SEMA3A (2%) | TACR3 (2.6%) | PLXNB1 (0.59%) | DMXL2 (3.1%) | PDE3A (5%) | ||||
| GNRH1 (2.1%) | SPRY4 (2%) | ANOS1 (1.7%) | SEMA4D (5.9%) | PROKR2 (2.3%) | ANOS1 (5%) | ||||
| GNRHR (2.1%) | FGF8 (1.7%) | EGF (4.6%) | POLR3B (2.3%) | GNRHR (5%) | |||||
| IL17RD (2.1%) | HS6ST1 (1.7%) | NRP2 (4.6%) | IL17RD (2.3%) | TAC3 (2.5%) | |||||
| JAG1 (2.1%) | WDR11 (1.7%) | B3GNT1 (3.9%) | SPRY4 (1.5%) | TACR3 (2.5%) | |||||
| MASTL (2.1%) | GNRH1 (1.7%) | IL17RD (3.9%) | SOX10 (1.5%) | AMHR2 (2.5%) | |||||
| NOS1 (2.1%) | KISS1 (1.7%) | NOS1 (3.9%) | SEMA7A (1.5%) | KISS1R (2.5%) | |||||
| NOTCH (2.1%) | FGF17 (0.9%) | ROBO3 (3.9%) | SEMA3A (1.5%) | SPRY4 (2.5%) | |||||
| NRP2 (2.1%) | PROK2 (0.9%) | DCC (3.3%) | POLR3A (1.5%) | ||||||
| PALM2 (2.1%) | KISS1R (0.9%) | MTOR (3.3%) | NSMF (1.5%) | ||||||
| PDE3A (2.1%) | TAC3 (0.9%) | SEMA7A (3.3%) | IGFALS (1.5%) | ||||||
| PLEHKA5 (2.1%) | DLX5 (2.6%) | GNRH1 (1.5%) | |||||||
| RD3 (2.1%) | GNRHR (2.6%) | FGF8 (1.5%) | |||||||
| TRAPPC9 (2.1%) | IGF1 (2.6%) | TAC3 (0.8%) | |||||||
| TSPAN11 (2.1%) | KISS1R (2.6%) | RNF216 (0.8%) | |||||||
| PAX6 (2.6%) | PNPLA6 (0.8%) | ||||||||
| AXL (2%) | OTX2 (0.8%) | ||||||||
| CNTN2 (2%) | IGSF1 (0.8%) | ||||||||
| EBF2 (2%) | FLRT3 (0.8%) | ||||||||
| EFNA5 (2%) | EBF2 (0.8%) | ||||||||
| MET (2%) | FGF17 (0.8%) | ||||||||
| PLXNA1 (2%) | |||||||||
| SEMA3A (2%) | |||||||||
| SLIT2 (2%) | |||||||||
| TACR3 (2%) | |||||||||
| FEZ1 (1.3%) | |||||||||
| CCKAR (1.3%) | |||||||||
| DCAF17 (1.3%) | |||||||||
| EDNRB (1.3%) | |||||||||
| EPHA5 (1.3%) | |||||||||
| GHR (1.3%) | |||||||||
| HGF (1.3%) | |||||||||
| NRP1 (1.3%) | |||||||||
| WDR11 (1.3%) | |||||||||
| CASR (0.7%) | |||||||||
| GH1 (0.7%) | |||||||||
| GNRH1 (0.7%) | |||||||||
| LEPR (0.7%) | |||||||||
| LIF (0.7%) | |||||||||
| NELF(NSMF) (0.7%) | |||||||||
| PROK2 (0.7%) | |||||||||
| STS (0.7%) | |||||||||
| TLE4 (0.7%) | |||||||||
| TYRO3 (0.7%) | |||||||||