Early-onset dysphagia and severe neurodevelopmental disorder as early signs in a patient with two novel variants in NARS1: a case report and brief review of the literature

Cesaroni, Carlo Alberto; Contrò, Gianluca; Spagnoli, Carlotta; Cancelliere, Federica; Caraffi, Stefano Giuseppe; Leon, Alberta; Stefanini, Camilla; Frattini, Daniele; Rizzi, Susanna; Cavalli, Anna; Garavelli, Livia; Fusco, Carlo

doi:10.1007/s10048-024-00760-0

Cited by 2 publications

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC–MS/MS

Mendes,

Wolf,

Rudinger-Thirion

et al. 2024

Nucleic Acids Research

View full text Add to dashboard Cite

In recent years, pathogenic variants in ARS genes, encoding aminoacyl-tRNA synthetases (aaRSs), have been associated with human disease. Patients harbouring pathogenic variants in ARS genes have clinical signs partly unique to certain aaRSs defects, partly overlapping between the different aaRSs defects. Diagnosis relies mostly on genetics and remains challenging, often requiring functional validation of new ARS variants. In this study, we present the development and validation of a method to simultaneously determine aminoacylation activities of all cytosolic aaRSs (encoded by ARS1 genes) in one single cell lysate, improving diagnosis in suspected ARS1 disorders and facilitating functional characterization of ARS1 variants of unknown significance. As proof of concept, we show enzyme activities of five individuals with variants in different ARS1 genes, demonstrating the usability and convenience of the presented method.

show abstract

Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC–MS/MS

Mendes,

Wolf,

Rudinger-Thirion

et al. 2024

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

Industrializing yeast as a drug repurposing platform for inherited metabolic diseases

Thevandavakkam,

Long,

Roel

et al. 2024

Preprint

View full text Add to dashboard Cite

SummaryThe development of therapies for rare diseases, particularly inherited metabolic disorders (IMDs), faces significant challenges due to the high cost and lengthy timelines involved. This study presents a yeast-based platform for drug repurposing that capitalizes on the remarkable similarity between yeast and human cellular pathways. This platform enables rapid, cost-effective screening of potential therapeutic compounds for rare diseases, offering a quick turnaround compared to traditional drug development processes. Utilizing a TargetMol library of comprising ∼50% nutraceuticals, our pipeline accelerates translation of promising drug repurposing hits into patient observational studies in as little as 6 months. We demonstrate the efficacy of this platform through three case studies in the context of IMDs, showcasing its potential to uncover novel treatments and reduce the time and expense associated with bringing therapies to patients with rare diseases.

show abstract

Early-onset dysphagia and severe neurodevelopmental disorder as early signs in a patient with two novel variants in NARS1: a case report and brief review of the literature

Cited by 2 publications

References 13 publications

Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC–MS/MS

Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC–MS/MS

Industrializing yeast as a drug repurposing platform for inherited metabolic diseases

Contact Info

Product

Resources

About