1. Novel partial loss-of-function variants in the tyrosyl-tRNA synthetase 1 (YARS1) gene involved in multisystem disease.
- Author
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Estève C, Roman C, DeLeusse C, Baravalle M, Bertaux K, Blanc F, Bourgeois P, Bresson V, Cano A, Coste ME, Delteil C, Lacoste C, Loosveld M, De Paula AM, Monnier AS, Secq V, Levy N, Badens C, and Fabre A
- Subjects
- Developmental Disabilities pathology, Failure to Thrive pathology, Female, Humans, Infant, Liver Diseases pathology, Loss of Function Mutation, Lung Diseases pathology, Developmental Disabilities genetics, Failure to Thrive genetics, Liver Diseases genetics, Lung Diseases genetics, Tyrosine-tRNA Ligase genetics
- Abstract
Cytoplasmic aminoacyl-tRNA synthetases (ARSs) are emerging as a cause of numerous rare inherited diseases. Recently, biallelic variants in tyrosyl-tRNA synthetase 1 (YARS1) have been described in ten patients of three families with multi-systemic disease (failure to thrive, developmental delay, liver dysfunction, and lung cysts). Here, we report an additional subject with overlapping clinical findings, heterozygous for two novel variants in tyrosyl-tRNA synthetase 1 (NM_003680.3(YARS1):c.176T>C; p.(Ile59Thr) and NM_003680.3(YARS1):c.237C>G; p.(Tyr79*) identified by whole exome sequencing. The p.Ile59Thr variant is located in the highly conserved aminoacylation domain of the protein. Compared to subjects previously described, this patient presents a much more severe condition. Our findings support implication of two novel YARS1 variants in these disorders. Furthermore, we provide evidence for a reduced protein abundance in cells of the patient, in favor of a partial loss-of-function mechanism., (Copyright © 2021. Published by Elsevier Masson SAS.)
- Published
- 2021
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