Other Ribosome Related Diseases

Ribosomopathies are inherited or sporadic disorders caused by the haploinsufficiency of genes encoding key factors in ribosome biogenesis or ribosome structural proteins. Such mutations often lead to tissue-specific developmental phenotypes, and the mechanisms underlying such tissue specificity have drawn considerable attention in light of the ubiquitous requirement for ribosomes in all cells. The list of conditions thought to involve or result from ribosomal stress is extensive and varied. Examples include Diamond-Blackfan anemia (DBA), Shwachman-Diamond syndrome, Treacher Collins syndrome, chromosome 5q syndrome, North American Indian childhood cirrhosis, and isolated congenital asplenia. These conditions constitute a heterogeneous group of clinical phenotypes that are linked by their common root in ribosomal dysfunction.

Fig. 1. Ribosome homeostasis and the translational cycle. (Mills, 2017)

Isolated Congenital Asplenia (ICA)

Patients with isolated congenital asplenia (ICA) are born without a spleen and display no other known developmental anomalies. Most patients with ICA, particularly the index cases, died in childhood from invasive bacterial disease. Defects in ribosome biogenesis or function capable of causing anemia and other hematologic phenotypes, defects in growth and development, and congenital anomalies, such as craniofacial defects and thumb. Expression studies indicated that the mutations carried by the patients cause autosomal dominant ICA by haploinsufficiency. RPSA encodes the ribosomal protein (RP) SA, a component of the small subunit of the ribosome. According to a previous report, heterozygosity for null RPSA alleles underlies AD ICA, possibly accounting for the strong purifying selection acting on these alleles in the population.

Fig. 2 Several mutations in RPSA display incomplete penetrance for ICA.²

North American Indian Childhood Cirrhosis (NAIC)

North American Indian Childhood Cirrhosis (NAIC) is an autosomal recessive cholestatic disorder caused by a missense mutation of CIRH1A, the human homolog of yeast Utp4. Unique among genes implicated in heritable cholangiopathies, CIRH1A encodes a member of the SSU processome and functions in ribosome biogenesis, as shown in yeast and mammalian cells. NAIC is distinguished from established ribosomopathies in that it has a single and unique clinical manifestation (cholestasis leading to biliary cirrhosis). Several causes have been proposed to account for the tissue-specific phenotypes associated with these disorders, including alternative splice forms, nonribosomal functions of the affected genes, and tissue-specific cofactors that mediate gene function. It is possible that Cirhin has non-ribosomal functions in biliary cells or hepatocytes, or that the NAIC mutation creates a CIRHIN protein with novel non-ribosomal functions.

Services at Creative Biolabs

Due to the ribosomes having important biological processes, any abnormal mutation will cause ribosomopathies. Going into the ribosome and trying to understand the scientific basis for these ribosomopathies are unavoidable research. Focusing on ribosome studies over years, Creative Biolabs has accumulated rich experience and strong foundations. Based on years of practice, we are capable of offering quality-assured ribosome relevant services including but not limited to:

• Ribosome Separation and Extraction Services
• Ribosome Analysis Services
• Ribosomal Marker Antibody Development Services

If you are interested in ribosome studies, or you would like to know more about our services, please feel free to contact us for more information.

References

1. Mills, E. W.; Green, R. Ribosomopathies: There's strength in numbers. Science. 2017, 358(6363).
2. Bolze, Alexandre, et al. "Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons." Proceedings of the National Academy of Sciences 115.34 (2018): E8007-E8016.