Ribosomopathies: New Therapeutic Perspectives
Abstract
:1. Introduction
2. The Main Mechanisms of Ribosomopathies
3. Ribosomopathies with Specific Corrections
3.1. Diamond–Blackfan Anemia (DBA)
3.2. Current Treatment
3.3. Therapeutic Perspectives
3.4. Dyskeratosis Congenita (DC)
3.5. Current Treatment
3.6. Therapeutic Perspectives
3.7. Treacher Collins Syndrome (TCS)
3.8. Current Treatment
3.9. Therapeutic Perspectives
3.10. Cartilage Hair Hypoplasia (CHH)
3.11. Current Treatment
3.12. Therapeutic Perspectives
3.13. Shwachman–Diamond Syndrome (SDS)
3.14. Current Treatment
3.15. Therapeutic Perspectives
3.16. 5q-Syndrome (5q)
3.17. Current Treatment
3.18. Therapeutic Perspectives
4. Ribosomopathies Treated with Generic Guidelines
4.1. North American Indian Childhood Cirrhosis (NAIC)
4.2. Isolated Congenital Asplenia (ICA)
4.3. Neurodevelopmental Disorders (ND)
5. Ribosomopathies that Remain Untreated
Bowen-Conradi Syndrome (BCS)
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Name | OMIM | Mutations | Phenotype | Current Treatment | Therapeutic Perspectives | |
---|---|---|---|---|---|---|
Diamond–Blackfan anemia | 105650 | •RPS7 | •RPL10A | •Anemia | •Chronic transfusions | •Danazol |
•RPS10 | •RPL11 | •Growth retardation | •Steroids | •L-leucine | ||
•RPS17 | •RPL15 | •Other defects ~30–50% | or | •Sotatercept | ||
•RPS19 | •RPL18 | •Craniofacial | • Hematopoietic Stem Cell Transplantation (HSCT) | •Trifluoperazine | ||
•RPS24 | •RPL19 | •Upper limb | •SMER28 | |||
•RPS26 | •RPL26 | •Heart malformations | •Eltrombopag | |||
•RPLP0 | •RPL34 | •Urinary system malformations | ||||
•RPL3 | •RPL35 | |||||
•RPL5 | •RPL35A | |||||
•RPL9 | •TSR2 | |||||
•RPL10 | ||||||
X-linked dyskeratosis congenita | 305000 | •DKC1 | •Skin pigmentation | •Chronic transfusions | •Eltrombopag | |
•Nail dystrophy | •HSCT | •Danazol | ||||
•Leucoplakia | •Regular examinations in | |||||
•Cytopenia | •Immunology | |||||
•Other defect >30% | •Dermatology | |||||
•Epiphora | •Neurology | |||||
•Learning difficulties/mental retardation | •Ophthalmology | |||||
•Pulmonary disease | •Otolaryngology | |||||
•Hyperhidrosis | •Dental | |||||
•Extensive dental carries/loss | •Cardiology | |||||
•Short stature | •Pulmonary | |||||
•Hair loss/grey hair or sparse eyelashes | ||||||
•Esophageal stricture | ||||||
•Hypogonadism/undescended testes | ||||||
•Urethral stricture/phimosis | ||||||
•Malignancy | ||||||
•Liver cirrhosis/adenoma | ||||||
•Abnormal bone trabeculation/osteoporosis | ||||||
Treacher Collins syndrome | 154500 | •Defects of craniofacial development | •Reconstructive surgery | •MG132 or Bortezomib | ||
•TCOF1 | •Conductive hearing loss | •Speech therapy | ||||
•POLR1C | •Palpebral fissures’ lateral downward sloping | |||||
•POLR1D | •Mandible hypoplasia | |||||
•Cleft palate | ||||||
Cartilage hair hypoplasia | 250250 | •RMRP | •Short stature | •Granulocyte Colony-Stimulating Factor (GCSF) | •Recombinant growth hormone | |
•Hypoplastic hair | •HSCT | •XAV939 | ||||
•Ligamentous laxity | ||||||
•Defective immunity | ||||||
•Hypoplastic anemia | ||||||
•Neuronal dysplasia of the intestine | ||||||
Shwachman–Diamond syndrome | 260400 | •Neutropenia | •Chronic transfusions | •Transforming Growth Factor beta (TGF-β) | ||
•SBDS | •Anemia | •Androgens | •Ataluren | |||
•DNAJC21 | •Thrombocytopenia | •HSCT | ||||
•EFL1 | •Bone marrow hypoplasia | •Reconstructive surgery | ||||
•SRP54 | •Skeletal abnormalities | •Pancreatic enzymes | ||||
•Pancreatic defects | •Vitamin supplements | |||||
•Dietary advice and surveillance | ||||||
5q-syndrome | 153550 | •RPS14 | •Macrocytic anemia | •Red blood cell transfusions | •Cenersen | |
•Erythroid hypoplasia | •Recombinant erythropoietin | •L-leucine | ||||
•Hypolobated micromegakaryocytes | •Thalidomide | |||||
•Retinoids | ||||||
•Chemotherapy | ||||||
•Hypomethylating agents | ||||||
•Bone marrow transplantation | ||||||
North American Indian | 604901 | •UTP4 | •Natal transient jaundice | •Liver transplantation | ||
childhood cirrhosis | •Biliary cirrhosis | |||||
•Portal hypertension | ||||||
Isolated congenital asplenia | 271400 | •RPSA | •Absence of spleen | •Anti-infection and antibiotic prophylaxis | ||
•Vaccination | ||||||
•Pneumococcal | ||||||
•Haemophilus influenzae type b | ||||||
•Meningococcal | ||||||
•Influenza | ||||||
Neurodevelopmental disorders | •RPL10 | •POLR1A | •Neural tube defects | •Mental health medication | ||
•RPS3 | •ERCC6 | •Microcephaly | •Speech therapy | |||
•LAS1L | •CSB | •Autism | •Pediatrics | |||
•SMN1 | •ERCC8 | •Schizophrenia | •Educational help | |||
•EXOSC3 | •CSA | •Epilepsy | ||||
•UBTF | •Cerebral palsy/periventricular leukomalacia | |||||
Bowen–Conradi syndrome | 211180 | •EMG1 | •Psychomotor defects | |||
•Growth retardation | ||||||
•Microcephaly | ||||||
•Micrognathia | ||||||
•Congenital vertical talus |
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Orgebin, E.; Lamoureux, F.; Isidor, B.; Charrier, C.; Ory, B.; Lézot, F.; Baud’huin, M. Ribosomopathies: New Therapeutic Perspectives. Cells 2020, 9, 2080. https://doi.org/10.3390/cells9092080
Orgebin E, Lamoureux F, Isidor B, Charrier C, Ory B, Lézot F, Baud’huin M. Ribosomopathies: New Therapeutic Perspectives. Cells. 2020; 9(9):2080. https://doi.org/10.3390/cells9092080
Chicago/Turabian StyleOrgebin, Emilien, François Lamoureux, Bertrand Isidor, Céline Charrier, Benjamin Ory, Frédéric Lézot, and Marc Baud’huin. 2020. "Ribosomopathies: New Therapeutic Perspectives" Cells 9, no. 9: 2080. https://doi.org/10.3390/cells9092080