A bi-allelic loss-of-function SARS1 variant in children with neurodevelopmental delay, deafness, cardiomyopathy, and decompensation during fever

Jean-Marie Ravel*, Natacha Dreumont, Pauline Mosca, Desiree E. C. Smith, Marisa I. Mendes, Arnaud Wiedemann, David Coelho, Emmanuelle Schmitt, Jean-Baptiste Rivière, Frédéric Tran Mau-Them, Julien Thevenon, Paul Kuentz, Marc Polivka, Sabine A. Fuchs, Gautam Kok, Christel Thauvin-Robinet, Jean-Louis Guéant, Gajja S. Salomons, Laurence Faivre, François Feillet*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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. 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.
Original languageEnglish
Pages (from-to)1576-1583
JournalHuman Mutation
Issue number12
Publication statusPublished - 1 Dec 2021

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