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. 2021 Dec 1;106(12):3202-3205.
doi: 10.3324/haematol.2021.279138.

Biallelic mutations in the SARS2 gene presenting as congenital sideroblastic anemia

Elia Colin  1 , Geneviève Courtois  2 , Chantal Brouzes  3 , Juliette Pulman  4 , Marion Rabant  5 , Agnès Rötig  4 , Hélène Taffin  6 , Mathilde Lion-Lambert  6 , Sylvie Fabrega  7 , Lydie Da Costa  8 , Mariane De Montalembert  9 , Rémi Salomon  6 , Olivier Hermine  10 , Lucile Couronné  11
Affiliations

Biallelic mutations in the SARS2 gene presenting as congenital sideroblastic anemia

Elia Colin et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Clinical and molecular findings of the proband. (A) Pedigree and segregation of the pathogenic SARS2 variants in the reported family. (B) Bone marrow aspiration from the proband showing the presence of ring sideroblasts on iron stain. (C) Sanger sequencing validation of SARS2 c.1031 G>A (p.R344Q) and c.1205 G>A (p.R402H) mutations detected by next generation sequencing. Red arrows indicate the position of the nucleotide’s substitution.
Figure 2.
Figure 2.
SARS2 depletion in early erythroblasts results in decreased proliferation rate and differentiation arrest due to increased apoptosis. (A) At day 5 (D5) of the first phase of culture, primary erythroid progenitors were transduced with scramble short hairpin RNA (shCTRL) or short hairpin RNA (shRNA) specifically targeting SARS2 (shSARS2). 48 hours later, cell proliferation of transduced cells was monitored for 150 hours by real-time videomicroscopy using the Incucyte® system. Results are represented as the fold increase of cell confluence normalized to T0. Error bars represent standard deviation (SD) from mean of 3 technical replicates. Data are representative of 3 independent experiments. (B) At the indicated days of the second phase of culture, shCTRL- and shSARS2-transduced cells were stained with an antibody directed against the GPA erythroid marker. The percentage of GPA positive cells was then assessed by flow cytometry. Error bars represent SD from mean of 3 independent experiments. (C) At day 6 (D6) of the second phase of culture, shCTRL- and shSARS2-transduced cells were stained with an antibody directed against Annexin V and with propidium iodide (PI). The percentage of apoptotic cells, defined as the percentage of the Annexin V positive cells amongst the PI negative population was assessed by flow cytometry. Error bars represent SD from mean of 3 independent experiments. P-values are determined by two-tailed t-test. ns: not significant; *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001.
Figure 3.
Figure 3.
Increased apoptosis in SARS2-depleted cells is mitochondria-mediated. (A) At day 4 of the second phase of culture, mitochondrial membrane potential was assessed by flow cytometry in scramble short hairpin RNA (shCTRL) and shSARS2-transduced cells after staining with the potentiometric DilC1(5) fluorescent dye. The percentage of depolarizing cells, defined as the Dilc1(5)low population was then assessed by flow cytometry. Data are representative of 2 independent experiments. (B) Western blot showing SARS2, cleaved caspase 3 and cleaved caspase 9 expression levels in shCTRL- and shSARS2-transduced cell at day 4 of the second phase of culture. Proteins levels were compared to b-actin expression. Data are representative of 2 independent experiments. (C) Representative western blot showing SARS2, COXII and ATP8 expression levels in shCTRL- and shSARS2-transduced cells at day 4 of the second phase of culture. Proteins levels were compared to b-actin expression.
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References

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