A bi-allelic loss-of-function SARS1 variant in children with neurodevelopmental delay, deafness, cardiomyopathy, and decompensation during fever
| Autor: | Jean-Marie Ravel, Jean-Louis Guéant, Natacha Dreumont, Marc Polivka, Jean-Baptiste Rivière, Frédéric Tran Mau-Them, Julien Thevenon, David Coelho, Gajja S. Salomons, Desirée E.C. Smith, Pauline Mosca, Emmanuelle Schmitt, Laurence Faivre, Gautam Kok, Marisa I. Mendes, Christel Thauvin-Robinet, Sabine A. Fuchs, Paul Kuentz, Arnaud Wiedemann, François Feillet |
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| Přispěvatelé: | Clinical chemistry, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Laboratory Genetic Metabolic Diseases, Amsterdam Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Ataxia
brain Cardiomyopathy SARS1 Loss of Heterozygosity Biology Amino Acyl-tRNA Synthetases chemistry.chemical_compound deafness death Genetics medicine Protein biosynthesis Missense mutation Humans Decompensation aminoacyl-tRNA synthetase Child tRNA Genetics (clinical) aminoacylation Aminoacyl tRNA synthetase medicine.disease Elongation factor chemistry intellectual disability Transfer RNA medicine.symptom Cardiomyopathies |
| Zdroj: | Human Mutation, 42(12), 1576-1583. Wiley-Liss Inc. Human mutation, 42(12), 1576-1583. Wiley-Liss Inc. Ravel, J-M, Dreumont, N, Mosca, P, Smith, D E C, Mendes, M I, Wiedemann, A, Coelho, D, Schmitt, E, Rivière, J-B, Tran Mau-Them, F, Thevenon, J, Kuentz, P, Polivka, M, Fuchs, S A, Kok, G, Thauvin-Robinet, C, Guéant, J-L, Salomons, G S, Faivre, L & Feillet, F 2021, ' A bi-allelic loss-of-function SARS1 variant in children with neurodevelopmental delay, deafness, cardiomyopathy, and decompensation during fever ', Human Mutation, vol. 42, no. 12, pp. 1576-1583 . https://doi.org/10.1002/humu.24285 |
| ISSN: | 1059-7794 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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