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, Год журнала: 2025, Номер 48(2)

Опубликована: Март 1, 2025

Язык: Английский

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Aminoacyl‐tRNA synthetase defects in neurological diseases

IUBMB Life, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 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

Язык: 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, Год журнала: 2024, Номер 5(3), С. 100324 - 100324

Опубликована: Июль 1, 2024

Язык: Английский

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

Genes, Год журнала: 2024, Номер 15(7), С. 951 - 951

Опубликована: Июль 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.

Язык: Английский

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Wars1 downregulation in hepatocytes induces mitochondrial stress and disrupts metabolic homeostasis

Metabolism, Год журнала: 2024, Номер 162, С. 156061 - 156061

Опубликована: Ноя. 7, 2024

Язык: Английский

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