scholarly journals Somatic uniparental disomy with a rare EFL1 variant causes Shwachman-Diamond syndrome through dysregulating ribosomal protein synthesis

2018 ◽  
Author(s):  
Sangmoon Lee ◽  
Chang Hoon Shin ◽  
Che Ry Hong ◽  
Jun-Dae Kim ◽  
Ah-Ra Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Rare Variant ◽  
Translational Control ◽  
Uniparental Disomy ◽  
Chromosome 15 ◽  
East Asians ◽  
Shwachman Diamond Syndrome ◽  
Ribosomal Protein Synthesis

We present three unrelated Korean Shwachman-Diamond syndrome (SDS) patients that carry an incomplete but identical homozygous EFL1 p.Thr1069Ala variant due to a bone marrow-specific mosaic uniparental disomy (UPD) in chromosome 15. This rare variant is found in 0.017% of East Asians and is asymptomatic in a heterozygous status, but harbors a hypomorphic effect, leading to 80S assembly of ribosomal protein (RP) transcripts. We propose a novel somatically-induced pathogenesis mechanism and EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.

scholarly journals Somatic uniparental disomy mitigates the most damaging EFL1 allele combination in Shwachman-Diamond syndrome

Blood ◽  
2021 ◽  
Author(s):  
Sangmoon Lee ◽  
Chang Hoon Shin ◽  
Jawon Lee ◽  
Seong Dong Jeong ◽  
Che Ry Hong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Translational Control ◽  
Uniparental Disomy ◽  
Ribosome Assembly ◽  
Chromosome 15 ◽  
80S Ribosome ◽  
Pathogenic Variants ◽  
Shwachman Diamond Syndrome ◽  
Allele Combination ◽  
Pronounced Inhibition

Shwachman-Diamond syndrome (SDS; OMIM: #260400) is caused by variants in SBDS (Shwachman-Bodian-Diamond syndrome gene), which encodes a protein that plays an important role in ribosome assembly. Recent reports suggest that recessive variants in EFL1 are also responsible for SDS. However, the precise genetic mechanism that leads to EFL1-induced SDS remains incompletely understood. Here we present three unrelated Korean SDS patients that carry biallelic pathogenic variants in EFL1 with biased allele frequencies, resulting from a bone marrow-specific somatic uniparental disomy (UPD) in chromosome 15. The recombination events generated cells that were homozygous for the relatively milder variant, allowing for the evasion of catastrophic physiological consequences. Still, the milder EFL1 variant was solely able to impair 80S ribosome assembly and induce SDS features in cell line and animal models. The loss of EFL1 resulted in a pronounced inhibition of terminal oligo-pyrimidine element-containing ribosomal protein transcript 80S assembly. Therefore, we propose a more accurate pathogenesis mechanism of EFL1 dysfunction that eventually leads to aberrant translational control and ribosomopathy.

scholarly journals TETRACYCLINE INHIBITION OF MYCOPLASMA RIBOSOMAL PROTEIN SYNTHESIS

1971 ◽  
Vol 24 (3) ◽  
pp. 185-188 ◽  
Author(s):  
CARL C. FRATERRIGO ◽  
D. PERLMAN
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Ribosomal Protein Synthesis

Translational regulation of ribosomal protein synthesis during xenopus development

1989 ◽  
Vol 27 ◽  
pp. 219
Author(s):  
B. Cardinali ◽  
C. Bagni ◽  
F. Amaldi ◽  
N. Campioni ◽  
P. Mariottini ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Translational Regulation ◽  
Xenopus Development ◽  
Ribosomal Protein Synthesis

Regulation of Ribosomal Protein Synthesis in Prokaryotes

2021 ◽  
Vol 55 (1) ◽  
pp. 16-36
Author(s):  
A. O. Mikhaylina ◽  
E. Y. Nikonova ◽  
O. S. Kostareva ◽  
S. V. Tishchenko
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Protein ◽  
Ribosomal Protein Synthesis
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