A bi-allelic loss-of-function SARS1 variant in children with neurodevelopmental delay, deafness, cardiomyopathy, and decompensation during fever
Ravel, Jean-Marie; Dreumont, Natacha; Mosca, Pauline; Smith, Desiree E C; Mendes, Marisa I; Wiedemann, Arnaud; Coelho, David; Schmitt, Emmanuelle; Rivière, Jean-Baptiste; Tran Mau-Them, Frédéric; Thevenon, Julien; Kuentz, Paul; Polivka, Marc; Fuchs, Sabine A; Kok, Gautam; Thauvin-Robinet, Christel; Guéant, Jean-Louis; Salomons, Gajja S; Faivre, Laurence; Feillet, François
(2021) Human mutation, volume 42, issue 12, pp. 1576 - 1583
(Article)
Abstract
Aminoacyl-tRNA synthetases (aaRS) are ubiquitously expressed enzymes responsible for ligating amino acids to their cognate tRNA molecules through an aminoacylation reaction. The resulting aminoacyl-tRNA is delivered to ribosome elongation factors to participate in protein synthesis. Seryl-tRNA synthetase (SARS1) is one of the cytosolic aaRSs and catalyzes serine attachment to tRNASer
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. SARS1 deficiency has already been associated with moderate intellectual disability, ataxia, muscle weakness, and seizure in one family. We describe here a new clinical presentation including developmental delay, central deafness, cardiomyopathy, and metabolic decompensation during fever leading to death, in a consanguineous Turkish family, with biallelic variants (c.638G>T, p.(Arg213Leu)) in SARS1. This missense variant was shown to lead to protein instability, resulting in reduced protein level and enzymatic activity. Our results describe a new clinical entity and expand the clinical and mutational spectrum of SARS1 and aaRS deficiencies.
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Keywords: SARS1, aminoacylation, aminoacyl‐tRNA synthetase, brain, deafness, death, intellectual disability, tRNA, Journal Article
ISSN: 1059-7794
Publisher: Wiley-Liss Inc.
Note: Publisher Copyright: © 2021 Wiley Periodicals LLC
(Peer reviewed)