Table 3.
New variants detected by NGS-based targeted sequencing in all patients
| Patient | Gene | Chr position | ID | Changes | MAF | In silico prediction |
|---|---|---|---|---|---|---|
| 1 | ECE1 | 1:g.21573855 A > G | rs1076669 | c.1013C > T/p.Thr338Ile | 0.04 | - / - |
| ECE1 | 1:g.21551614 G > A | rs3026905 | c.2004 + 129C > T | 0.02 | - | |
| 2 | GFRA3 | 5:g.137588322 C > T | - | c.*335 G > A | <0.01 | Low activity region |
| RET | 10:g.43600210delGCACAGTCA | rs546164092 | c.625 + 2134delGCACAGTCA | 0.004 | Enhancer | |
| RET | 10:g.43600325delCC | rs144431581 | c.625 + 2244delCC | >0.05 | Enhancer | |
| GFRA1 | 10:g.117884822 T > A | - | c.665A > T/p.Gln222Leu | <0.01 | - / + | |
| 3 | SEMA3D | 7:g.84651849 G > T | rs141893504 | c.1272C > A/p.His424Gln | <0.01 | + / + |
| GFRA1 | 10:g.118030415 A > T | rs8192662 | c.253 T > A/p.Tyr85Asn | 0.02 | + / + | |
| EDNRB | 13:g.78493201 C > T | - | c.-51-442 C > T | <0.01 | Promoter | |
| GDNF | 5:g.37835932 G > A | - | c.-26-1008 G > A | - | - | |
| 4 | ECE1 | 1:g.21564631 C > T | rs141146885 | c.1376G > A/p.Ser459Asn | <0.01 | - / - |
| 5 | PHOX2B | 4:g.41749629 A > G | rs191239994 | c.242-76 T > C | <0.01 | Enhancer |
| SEMA3C | 7:g.80378343 T > A | rs201228749 | c.1713A > T/p.Ala571Ala | - | New splicing site | |
| GFRA2 | 8:g.21640172 C > T | - | c.280C > T/p.Arg94Cys | <0.01 | + / + | |
| 6 | PHOX2B | 4:g.41747630 G > A | rs186778106 | c.*194C > A | 0.01 | Enhancer |
| NRG1 | 8:g.32406656 C > T | rs148585725 | c.100 + 312C > T | 0.01 | Promoter /CTCF binding site | |
| NRG1 | 8:g.32617713C > T | rs79223941 | c.1086-5C > T | 0.01 | - | |
| 7 | NRG1 | 8:g.32611970 G > T | rs74942016 | c.772G > T/p.Val258Leu | 0.02 | + / + |
| 8 | GFRA1 | 10:g.118030415 A > T | rs8192662 | c.253 T > A/p.Tyr85Asn | 0.02 | + / + |
| 10 | NRG1 | 8:g.32611970 G > T | rs74942016 | c.772G > T/p.Val258Leu | 0.02 | + / + |
| ECE1 | 1:g.21571475 G > A | rs28368004 | c.1242 + 7C > T | 0.01 | CTCF binding site | |
| GFRA1 | 10:g.118031734 G > C | rs45568534 | c.-193C > G | 0.01 | Enhancer | |
| 11 | EDNRB | 13:g.78492763 G > C | - | c.*988C > G | - | Predicted promoter |
| NTF3 | 12:g.5541624 C > G | rs71578945 | c.18 + 116C > G | <0.01 | Enhancer |
Description of all new variants found in this study, except for patient 9, who was not found to carry any new additional variant by NGS
In silico prediction: amino acidic changes (− / −) benign for SIFT and Polyphen; (− / +) damaging in one; (+ / +) damaging in both
Non-coding regions evaluated by the ENCODE project database