Genetics of the Ribosomopathies


Ribosomopathies refer collectively to a group of disorders characterised by disruption of ribosome synthesis. Classically, these are rare genetic syndromes with developmental abnormalities, often involving abnormal blood cell production, as seen in Diamond Blackfan anaemia, the 5q‐myelodysplastic syndrome and Shwachman‐Diamond syndrome or causing craniofacial anomalies (Treacher Collins syndrome). However, research has recognised several new putative ribosomopathies (Bowen‐Conradi syndrome and North American Indian childhood cirrhosis), and new revelations may force the reclassification of some older disorders (dyskeratosis congenita and cartilage hair hypoplasia). Finally, some, but not all, ribosomopathies predispose patients to solid tumours or haematologic malignancies. Here, we critically review the underlying genetics in old and new ribosomopathies and examine the pathophysiologic consequences of aberrant ribosome biogenesis.

Key Concepts:

  • Ribosomopathies refer collectively to a group of disorders characterised by disruption of ribosome synthesis.

  • Most ribosomopathies are rare genetic syndromes with developmental abnormalities, often involving abnormal blood cell production or causing craniofacial anomalies.

  • There are several new putative ribosomopathies and the classification of some disorders is in flux.

  • Diamond‐Blackfan anemia and Treacher Collins syndrome are two well‐described ribosomopathies that share pathophysiologic similarities but have different clinical manifestations for the most part.

  • Some, but not all, ribosomopathies predispose patients to solid tumours or haematologic malignancies.

Keywords: ribosomopathies; developmental disorders; ribosomal stress; p53; bone marrow failure syndromes

Figure 1.

Ribosomopathies and model of pre‐rRNA processing. Ribosomopathies are noted in green (established), red (disputed) and blue (putative), depending on the degree of confidence in their role in ribosome synthesis.



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Further Reading

Goldberg TA, Singh S, Solaimanzadeh J et al. (2011) Knockdown of p53 improves hematopoietic and erythroid differentiation defects in mouse embryonic stem cell models of Diamond Blackfan anemia. Blood 118: 330.

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Liu, Johnson M, Lipton, Jeffrey M, and Ellis, Steven R(Feb 2013) Genetics of the Ribosomopathies. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023863]