ribosomopathies

Ribosomopathies comprise a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes.

Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia.

Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes:
 Shwachman-Diamond syndrome
 dyskeratosis congenita
 cartilage hair hypoplasia
 Treacher-Collins Syndrome.

In addition, the 5q- syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, leading to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia.

Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies.

The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies.

References

 Ribosomopathies: human disorders of ribosome dysfunction. Narla A, Ebert BL. Blood. 2010 Mar 1. PMID: 20194897