@article {1011,
	title = {Germline SAMD9L truncation variants trigger global translational repression.},
	journal = {J Exp Med},
	volume = {218},
	year = {2021},
	month = {2021 May 03},
	abstract = {<p>SAMD9L is an interferon-induced tumor suppressor implicated in a spectrum of multisystem disorders, including risk for myeloid malignancies and immune deficiency. We identified a heterozygous de novo frameshift variant in SAMD9L in an infant with B cell aplasia and clinical autoinflammatory features who died from respiratory failure with chronic rhinovirus infection. Autopsy demonstrated absent bone marrow and peripheral B cells as well as selective loss of Langerhans and Purkinje cells. The frameshift variant led to expression of a truncated protein with interferon treatment. This protein exhibited a gain-of-function phenotype, resulting in interference in global protein synthesis via inhibition of translational elongation. Using a mutational scan, we identified a region within SAMD9L where stop-gain variants trigger a similar translational arrest. SAMD9L variants that globally suppress translation had no effect or increased mRNA transcription. The complex-reported phenotype likely reflects lineage-dominant sensitivities to this translation block. Taken together, our findings indicate that interferon-triggered SAMD9L gain-of-function variants globally suppress translation.</p>},
	issn = {1540-9538},
	doi = {10.1084/jem.20201195},
	author = {Allenspach, Eric J and Soveg, Frank and Finn, Laura S and So, Lomon and Gorman, Jacquelyn A and Rosen, Aaron B I and Skoda-Smith, Suzanne and Wheeler, Marsha M and Barrow, Kaitlyn A and Rich, Lucille M and Debley, Jason S and Bamshad, Michael J and Nickerson, Deborah A and Savan, Ram and Torgerson, Troy R and Rawlings, David J}
}
