Table 2.
Evaluation of drug-induced readthrough over nonsense mutations in FVIII, FIX and FVII deficiencies.
| Mutation (HGVS)* | Mutation (Legacy)** | Sense Codon | PTC Sequence Context | Predicted Amino Acid Insertion† | Cellular Model | Mouse Model | Patients | Ref | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug | Response | Drug | Response | Drug | Response | |||||||
| F8 | p.R446X | R427X | CGA | UGA-U | W / C / R | - | - | - | - | Gentamycin | No | [158] |
| p.S1414X | S1395X | TCA | UAA-U | Y / Q / K | - | - | - | - | Gentamycin | 1.6% | [158] | |
| p.R2135X | R2116X | CGA | UGA-G | W / C / R | - | - | - | - | Gentamycin | No | [158] | |
| F9 | p.G21X | G(-26)X | GGA | UGA-U | W / C / R | Geneticin | 4% | - | - | - | - | [160] |
| p.R75X | R29X | CGA | UGA-G | W / C / R | Geneticin | No | Geneticin / Gentamycin | No | - | - | [159,161] | |
| p.L103X | L57X | UUA | UAA-A | Y / Q / K | Geneticin | No | - | - | - | - | [161] | |
| p.R162X | R116X | CGA | UGA-C | W / C / R | Geneticin | ~1% | - | - | - | - | [161] | |
| p.W240X | R194X | UGG | UGA-C | W / C / R | Geneticin | 5–6% | - | - | - | - | [161] | |
| p.R294X | R248X | CGA | UGA-A | W / C / R | Geneticin | 0.5–1% | - | - | - | - | [161] | |
| p.R298X | R252X | CGA | UGA-A | W / C / R | Geneticin | No | - | - | Gentamycin | No | [158,161] | |
| p.R379X | R333X | CGA | UGA-G | W / C / R | Geneticin | 1% | - | - | Gentamycin | 2% / No | [158,162] | |
| p.Q370X | R324X | CAG | UAG-U | Y / Q / K | Geneticin | ~1% | - | - | - | - | [161] | |
| p.R384X | R338X | CGA | UGA-U | W / C / R | Geneticin | 7-8% | Geneticin / Gentamycin | - | - | - | [159,161] | |
| F7 | p.S112X | S52X | UCA | UGA-A | W / C / R | Geneticin | 2–3% | - | - | - | - | [163] |
| p.C132X | C72X | UGC | UGA-C | W / C / R | Geneticin | 12–13% | - | - | - | - | [163] | |
| p.K376X | K316X | AAG | UAG-G | Y / Q / K | Geneticin / Gentamycin | >3% / >2% | - | - | Gentamycin | sub-therapeutic | [164,165] | |
| p.W424X | W364X | UGG | UGA-G | W / C / R | Geneticin / Gentamycin | >3% / >2% | - | - | Gentamycin | sub-therapeutic | [164,165] | |
* Based on Human Genome Variation Society (HGVS) nomenclature numbering initiation methionine as +1 residue; ** Based on amino acid numbering of the secreted mature protein; † Predicted amino acid insertions as a function of the stop codon type.