Abnormal
ribosome biogenesis is linked to several human
genetic diseases. Ribosomopathy has been linked to skeletal muscle atrophy, and underpins most
Diamond–Blackfan anemia (DBA), and
ANE syndrome (ANES). The associated
chromosome,
OMIM genotype,
phenotype, and possible disruption points are shown: Several ribosomopathies share features such as
inherited bone marrow failure, which is characterized a reduced number of blood cells and by a predisposition to
cancer. Other features can include skeletal abnormalities and growth retardation. However, clinically these diseases are distinct, and do not show a consistent set of features.
Diamond–Blackfan anemia With the exception of rare
GATA1 genotypes,(cite)
Diamond–Blackfan anemia (DBA) arises from a variety of mutations that cause ribosomopathies.
Dyskeratosis congenita The
X-linked subtype of
dyskeratosis congenita (DKCX)
Shwachman–Diamond syndrome Shwachman–Diamond syndrome (SDS) is caused by bi-allelic mutations in the
SBDS protein that affects its ability to couple GTP hydrolysis by the GTPase EFL1 to the release of
eIF6 from the 60S subunit. Clinically, SDS affects multiple systems, causing bony abnormalities, and pancreatic and neurocognitive dysfunction. SBDS associates with the 60S subunit in human cells and has a role in subunit joining and translational activation in yeast models.
5q- myelodysplastic syndrome 5q- myelodysplastic syndrome (MDS) is associated with acquired haplo-insufficiency of
RPS14, a component of the
eukaryotic small ribosomal subunit (40S). RPS14 is critical for 40S assembly, and depletion of RPS14 in human
CD34(+) cells is sufficient to recapitulate the 5q- defect of
erythropoiesis with sparing of
megakaryocytes.
Treacher Collins syndrome Treacher Collins syndrome (TCS)
Cartilage–hair hypoplasia Cartilage–hair hypoplasia (CHH) - some sources list confidently as ribosomopathy, others question
North American Indian childhood cirrhosis NAIC is an autosomal recessive abnormality of the
UTP4 gene, which codes for cirhin.
Neonatal jaundice advances over time to biliary
cirrhosis with severe liver
fibrosis.
Isolated congenital asplenia Bowen–Conradi syndrome Bowen–Conradi syndrome (BCS or BWCNS) is an
autosomal recessive abnormality of the
EMG1 gene, which plays a role in
small ribosomal subunit (SSU) assembly. Most affected children have been from North American
Hutterite families, but BWCNS can affect other population groups. Skeletal dysmorphology is seen and severe prenatal and postnatal growth failure usually leads to death by one year of age.
Other Familial colorectal cancer type X Unlike the mutations of the 5 genes associated with
DNA mismatch repair, which are associated with
Lynch syndrome with hereditary nonpolyposis colorectal cancer (HNPCC) due to
microsatellite instability, familial colorectal cancer (CRC) type X (FCCX) gives rise to HNPCC despite microsatellite stability. FCCX is most likely etiologically heterogeneous but
RPS20 may be implicated in some cases. ==p53==