Table 2.
Mutations in genes that predispose to NB
| Genea | Mutation/alteration | Domain | Reference(s) |
|---|---|---|---|
| ALK | R1275Q | Kinase | 69–73 |
| L1204F | Kinase | ||
| R1192P | Kinase | ||
| I1183T | Kinase | ||
| T1151R | Kinase | ||
| G1128A | Kinase | ||
| PHOX2B | 676delG | NPARM | 79, 80, 83, 85, 86 |
| R100L | NPARM | ||
| R141G | NPARM | ||
| G197D | NPARM | ||
| PARM-28–33+ | PARM | ||
| TP53 | R337H, (other?) | NLS domain-1 | 102 |
| CDKN1C | Inactivating | Nonfocal | 103, 104 |
| RASopathiesb | Activating | Hotspots | 90–96 |
Abbreviations: NLS, nuclear localization sequence; NPARM, nonpolyalanine repeat mutation; PARM, polyalanine repeat expansion mutation.
a
Other genes have been implicated in NB predisposition, including GALNT14 and SDHB, but the data on prevalence and relative risk are limited at this time.
b
Costello syndrome is cause by mutations in HRAS, and Noonan syndrome is caused by mutations in PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, or MEK1. Costello syndrome is the only RASopathy that warrants NB screening at the present time. However, patients with Costello syndrome may have elevated catecholamine metabolites, so only very high levels or significantly rising levels would warrant further evaluation for NB (92).