Bi-allelic KARS1 pathogenic variants affecting functions of cytosolic and mitochondrial isoforms are associated with a progressive and multisystem disease.

"CONFLICT OF INTERESTS All the authors declare that there are no conflicts of interests."

"We are grateful to patients and their parents for their participation to the study. This study was supported by Telethon Foundation, Telethon Undiagnosed Diseases Program (TUDP, GSP15001), and by the Italian Ministry of Health, grant RF‐2016‐02361241 (to P.G.). Case 3 was ascertained in the Duke Genome Sequencing Clinic, which is supported by Duke University Health System. This study was in part generated within the European Reference Network ITHACA. The study benefited from the equipment and framework of the COMP‐HUB Initiative funded by the ‘Departments of Excellence’ program of the Italian Ministry for Education, University and Research (MIUR, 2018‐2022). We acknowledge the contribution of the DECIPHER Consortium. The DECIPHER study makes use of data generated by the DECIPHER community. A full list of centers who contributed to the generation of the data is available from decipher.sanger.ac.uk and via email from decipher@sanger.ac.uk. Funding for the project was provided by the Wellcome Trust. This publication was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH."