Setting the Stage for Treatment of Aminoacyl‐tRNA Synthetase (ARS)1‐Deficiencies: Phenotypic Characterization and a Review of Treatment Effects

Journal of Inherited Metabolic Disease, Journal Year: 2025, Volume and Issue: 48(2)

Published: March 1, 2025

Language: Английский

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Aminoacyl‐tRNA synthetase defects in neurological diseases

IUBMB Life, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 2, 2024

Abstract Aminoacyl‐tRNA synthetases (aaRSs) are essential enzymes to support protein synthesis in all organisms. Recent studies, empowered by advancements genome sequencing, have uncovered an increasing number of disease‐causing mutations aaRSs. Monoallelic aaRS typically lead dominant peripheral neuropathies such as Charcot–Marie–Tooth (CMT) disease, whereas biallelic often impair the central nervous system (CNS) and cause neurodevelopmental disorders. Here, we review recent progress disease onsets, molecular basis, potential therapies for diseases caused mutations, with a focus on cytoplasmic

Language: Английский

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A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants

Human Genetics and Genomics Advances, Journal Year: 2024, Volume and Issue: 5(3), P. 100324 - 100324

Published: July 1, 2024

Language: Английский

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Novel Cases of Non-Syndromic Hearing Impairment Caused by Pathogenic Variants in Genes Encoding Mitochondrial Aminoacyl-tRNA Synthetases

Genes, Journal Year: 2024, Volume and Issue: 15(7), P. 951 - 951

Published: July 19, 2024

Dysfunction of some mitochondrial aminoacyl-tRNA synthetases (encoded by the KARS1, HARS2, LARS2 and NARS2 genes) results in a great variety phenotypes ranging from non-syndromic hearing impairment (NSHI) to very complex syndromes, with predominance neurological signs. The diversity roles that are played these moonlighting enzymes fact most pathogenic variants missense affect different domains proteins diverse compound heterozygous combinations make it difficult establish genotype–phenotype correlations. We used targeted gene-sequencing panel investigate presence those four genes cohorts 175 Spanish 18 Colombian familial cases non-DFNB1 autosomal recessive NSHI. Disease-associated were found five cases. Five mutations novel as follows: c.766C>T c.475C>T, c.728A>C c.1012G>A c.795A>G LARS2. provide audiograms patients at ages document evolution loss, which is mostly prelingual progresses moderate/severe profound, middle frequencies being more severely affected. No additional clinical sign was observed any affected subject. Our confirm involvement KARS1 DFNB89 NSHI, for until now there limited evidence.

Language: Английский

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Wars1 downregulation in hepatocytes induces mitochondrial stress and disrupts metabolic homeostasis

Metabolism, Journal Year: 2024, Volume and Issue: 162, P. 156061 - 156061

Published: Nov. 7, 2024

Language: Английский

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