Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia
Abstract
1. Introduction
2. Overview of the Nonsense Suppression Therapeutic Approach
3. Compounds with Nonsense Suppression Properties
3.1. Aminoglycosides
3.2. Ataluren (PTC124)
3.3. Novel Small Compounds with Nonsense Suppression Properties
4. Negative Modulation of Nonsense Mediated mRNA Decay
5. β-Thalassemia
5.1. Nonsense Mutations and Nonsense Mediated mRNA Decay in β-Thalassemia
5.2. Readthrough Approach for β-Thalassemia
6. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
Abbreviations
APC | adenomatous polyposis coli |
CF | Cystic Fibrosis |
CFTR | cystic fibrosis trans-membrane conductance regulator |
DMD | Duchenne muscular dystrophy |
HbA | Adult Hemoglobin (HbA) |
HBE | human bronchial epithelial |
HSs | hypersensitive sites |
LCR | locus control region |
LSD | lysosomal storage diseases |
MPS I-H | mucopolysaccharidosis I-Hurler |
NMD | Nonsense mRNA-mediated decay |
PTCs | premature termination codons |
UTRs | untranslated regions |
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Nonsense Mutation | Sense/Nonsense Codon | Nucleotide Substitution | Frequency | NMD Activation | Reference |
---|---|---|---|---|---|
β°15 | TGG/TAG | G→A | Bangladesh 10% | NO | 97 |
β°15 | TGG/TGA | G→A | Portugal 11.79% Russia 6.45% | NO | 98 |
β°17 | AAG/TAG | A→T | Thailand 18.56% China 14.1% | NO | 98 |
β°22 | GAA/TAA | G→T | La Réunion (one case) | NO | 98 |
β°26 | GAG/TAG | G→T | Thailand 0.12% | YES | 99 |
β°35 | TAC/TAA | C→A | Thailand 1.22% | YES | 99 |
β°37 | TGG/TAG | G→A | Afghanistan | YES | 100 |
β°37 | TGG/TGA | G→A | Arab countries 18.6% | YES | 101 |
β°39 | CAG/TAG | C→T | Italy 66.84%; Argentina 47.06%; Portugal 34.9%; England 34.78% | YES | 102 |
β°43 | GAG/TAG | G→T | Singapore 0.75%; Thailand 0.37% | YES | 103 |
β°59 | AAG/TAG | A→T | Italian-American Family | YES | 104 |
β°61 | AAG/TAG | A→T | USA (one case) | YES | 105 |
β°90 | GAG/TAG | G→T | Japan 13.8% | YES | 99 |
β°112 | TGT/TGA | T→A | Slovakia (one case) | YES | 96 |
β°121 | GAA/TAA | G→T | Czechoslovakia 11.83% England 13.04% | YES | 106 |
β°127 | CAG/TAG | C→T | England (one case) | NO | 107 |
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Borgatti, M.; Altamura, E.; Salvatori, F.; D’Aversa, E.; Altamura, N. Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia. J. Clin. Med. 2020, 9, 289. https://doi.org/10.3390/jcm9020289
Borgatti M, Altamura E, Salvatori F, D’Aversa E, Altamura N. Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia. Journal of Clinical Medicine. 2020; 9(2):289. https://doi.org/10.3390/jcm9020289
Chicago/Turabian StyleBorgatti, Monica, Emiliano Altamura, Francesca Salvatori, Elisabetta D’Aversa, and Nicola Altamura. 2020. "Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia" Journal of Clinical Medicine 9, no. 2: 289. https://doi.org/10.3390/jcm9020289
APA StyleBorgatti, M., Altamura, E., Salvatori, F., D’Aversa, E., & Altamura, N. (2020). Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia. Journal of Clinical Medicine, 9(2), 289. https://doi.org/10.3390/jcm9020289