Table 1.
Pathologies linked to mutations in genes encoding ribosomal proteins or ribosomal assembly factors (ribosomopathies).
| Disease Manifestation/Clinical Features | Frequency | Inheritance | Genes Involved in Ribosome Biogenesis | Proteins | Functional Validation of Impact on Ribosome Biogenesis | % of Patients | References | |
|---|---|---|---|---|---|---|---|---|
| Patient Cells | Models * | |||||||
| Diamond-Blackfan anemia | ||||||||
| Aregenerative macrocytic anemia, high eADA levels, short stature, craniofacial and upper limb anomalies, heart or genitourinary malformations, predisposition to MDS, AML, and solid tumors | 1:150,000–200,000 births | Autosomal dominant | RPS7 | RPS7 | no | yes | <0.1% | [109,120,121,122] |
| RPS10 | RPS10 | yes | yes | 3% | [123] | |||
| RPS15A | RPS15A | yes | yes | <1% | [124] | |||
| RPS17 | RPS17 | yes | yes | 1% | [109,125,126,127,128] | |||
| RPS19 | RPS19 | yes | yes | 25% | [41,42,129] | |||
| RPS24 | RPS24 | yes | yes | 2.4% | [110,130] | |||
| RPS26 | RPS26 | yes | yes | 6.6% | [123] | |||
| RPS27 | RPS27 | no | yes | <0.1% | [120] | |||
| RPS28 | RPS28 | no | yes | <0.1% | [114] | |||
| RPS29 | RPS29 | yes | yes | <0.1% | [131] | |||
| RPL5 | RPL5 | yes | yes | 7% | [109] | |||
| RPL11 | RPL11 | yes | yes | 5% | [109] | |||
| RPL15 | RPL15 | yes | yes | <0.5% | [132] | |||
| RPL18 | RPL18 | yes | yes | <0.1% | [133] | |||
| RPL26 | RPL26 | yes | yes | <0.1% | [134] | |||
| RPL27 | RPL27 | yes | yes | <0.1% | [120] | |||
| RPL31 | RPL31 | yes | yes | <0.1% | [113] | |||
| RPL35 | RPL35 | yes | yes | <1% | [133] | |||
| RPL35A | RPL35A | yes | yes | 3% | [135] | |||
| One family | X-linked recessive | TSR2 | TSR2 | no | yes | <0.1% | [114] | |
| 5q-syndrome | ||||||||
| MDS, severe macrocytic anemia | 10–15% of patients with MDS or AML | Sporadic | RPS14 | RPS14 | yes | yes | 100% | [136] |
| Isolated congenital asplenia | ||||||||
| Absence of spleen, high susceptibility to infections | 1:60,000 births | Autosomal dominant | RPSA | RPSA | no | yes | 100% | [137] |
| Other syndromes caused by RP mutations | ||||||||
| Intellectual disability, autism, microcephaly, hearing loss | Two patients | Autosomal dominant | RPS23 | RPS23 | yes | yes | n.a. | [138] |
| Autism, microcephaly, mental retardation, growth retardation, seizures, skeletal malformations | Three families/Nine patients | RPL10 | RPL10 | no | yes | n.a. | [139,140,141] | |
| Autism, microcephaly | Two families/Four patients | RPL10 | RPL10 | no | n.a. | [142,143] | ||
| Intellectual disability, epilepsy | One patient | RPL10 | RPL10 | no | n.a. | [144] | ||
| Schwachman-Diamond anemia | ||||||||
| Neutropenia, exocrine pancreatic dysfunction, metaphyseal dysplasia, osteopenia, mild mental retardation, high predisposition to MDS and AML | 1:77,000 births | Autosomal recessive | SBDS | SBDS | yes | yes | >95% | [145,146] |
| DNAJC21 | DNAJC21 ** | yes | yes | 2% | [147,148,149] | |||
| EFL1 | EFL1 | no | yes | <0.5% | [149,150] | |||
| Bowen-Conradi Syndrome | ||||||||
| Growth retardation, psychomotor delay, microcephaly, micrognatia, joint contractures, rockerbottom feet | 1:355 in the Hutterite populations | Autosomal recessive | EMG1 | EMG1 | no | yes | 100% | [151,152,153] |
| North American Indian chilhood cirrhosis | ||||||||
| Cirrhosis | 1:250 in the Ojibway-Cree First Nations population | Autosomal recessive | CIRH1A | hUTP4 | no | yes | 100% | [154,155] |
| Familial Aplasia Cutis Congenita | ||||||||
| Scalp skin defect | 1 patient | Autosomal dominant | BMS1 | BMS1 | yes | yes | n.a. | [156] |
| Cartilage-hair hypoplasia | ||||||||
| Hypoplastic macrocytic anemia, neutropenia, defective T-cell, response, short limb dwarfism, fine, sparse hair, skeletal abnormalities, nail dysplasia, gastrointestinal malabsorption, abnormal dentition, predisposition to non-Hodgkin lymphomas and other cancers | 1–2:1000 in the Amish population, 1:23,000 in the Finnish population | Autosomal recessive | RMRP | - | yes | yes | 100% | [61,157] |
| Diskeratosis congenita and Hoyeraal-Hreidarsson syndrome | ||||||||
| Bone marrow failure, pancytopenia, aplastic anemia, mucocutaneous defects, nail dystrophy, developmental delay, pulmonary fibrosis, reduced telomere length, cancer predisposition, immunodeficiency | 1:1,000,000 births | X-linked recessive | DKC1 | Dyskerin | no | yes | 25% | [158,159] |
| Autosomal recessive | NOP10 | NOP10 | no | no | <1% | [160] | ||
| NHP2 | NHP2 | no | no | <1% | [161] | |||
| PARN | PARN | yes | yes | <1% | [162,163] | |||
| Treacher-Collins syndrome | ||||||||
| Severe craniofacial defects, mental retardation | 1:10,000–50,000 births | Autosomal dominant | TCOF1 | Treacle | no | yes | 78–93% | [164] |
| Autosomal dominant or recessive | POLR1D | RPA16 | no | yes | 8% *** | [165,166,167] | ||
| autosomal recessive | POLR1C | RPA39 | no | yes | [165] | |||
| Other RNA polymerase I-related diseases | ||||||||
| Acrofacial dysostosis | Three patients | Autosomal dominant | POLR1A | RPA194 | no | yes | n.a. | [168] |
| Severe neurodegenerative disease, psychomotor retardation, intellectual disability | Two patients | POLR1A | RPA194 | no | n.a. | [169] | ||
* Tissue culture of mammalian cells or vertebrate models; ** DnaJ homolog subfamily C member 21; *** Combined % for POLR1D and POLR1C mutations. eADA, erythrocyte adenosine deaminase; MDS, Myelodysplastic syndrome; AML, Acute myeloid leukemia; n.a., not available.