{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:32Z","timestamp":1785183872909,"version":"3.55.0"},"reference-count":24,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T00:00:00Z","timestamp":1606608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS), which activates and joins lysine with its corresponding transfer RNA (tRNA) through the ATP-dependent aminoacylation of the amino acid. KARS gene mutations have been linked to diverse neurologic phenotypes, such as neurosensorial hearing loss, leukodystrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, the impairment of the mitochondrial respiratory chain, and hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene and, in addition to the case report, the paper reviews the literature for other cases of KARS1-associated leukodystrophy.<\/jats:p>","DOI":"10.3390\/genes11121437","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T21:55:31Z","timestamp":1606686931000},"page":"1437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Progressive Early-Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9775-8656","authenticated-orcid":false,"given":"Adriana","family":"Vargas","sequence":"first","affiliation":[{"name":"Cl\u00ednica Universidad de La Sabana, Km 7, Autopista Norte de Bogot\u00e1, Ch\u00eda 250001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Rojas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Pontificia Universidad Javeriana, Cra 7a N\u00b0 40 B-36, Bogot\u00e1 110231, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-2735","authenticated-orcid":false,"given":"Ivan","family":"Aivasovsky","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad de La Sabana, Km 7, Autopista Norte de Bogot\u00e1, Ch\u00eda 250001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-6118","authenticated-orcid":false,"given":"Sergio","family":"Vergara","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad de La Sabana, Km 7, Autopista Norte de Bogot\u00e1, Ch\u00eda 250001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Castellanos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad de La Sabana, Km 7, Autopista Norte de Bogot\u00e1, Ch\u00eda 250001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Prieto","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad de La Sabana, Km 7, Autopista Norte de Bogot\u00e1, Ch\u00eda 250001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-6258","authenticated-orcid":false,"given":"Luis","family":"Celis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universidad de La Sabana, Km 7, Autopista Norte de Bogot\u00e1, Ch\u00eda 250001, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mirande, M. (2017). The Aminoacyl-tRNA Synthetase Complex. Sub-Cellular Biochemistry, Springer. Available online: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28271488.","DOI":"10.1007\/978-3-319-46503-6_18"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1177\/0883073814553272","article-title":"Congenital Visual Impairment and Progressive Microcephaly Due to Lysyl\u2013Transfer Ribonucleic Acid (RNA) Synthetase (KARS) Mutations","volume":"30","author":"McMillan","year":"2014","journal-title":"J. Child Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"787956","DOI":"10.1155\/2014\/787956","article-title":"The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes","volume":"2014","author":"Diodato","year":"2014","journal-title":"Int. J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/humu.23335","article-title":"Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: Potential pathogenic mechanism","volume":"38","author":"Zhou","year":"2017","journal-title":"Hum. Mutat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1101\/gr.9.8.689","article-title":"Evolution of Aminoacyl-tRNA synthetases-analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events","volume":"9","author":"Wolf","year":"1999","journal-title":"Genome Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/j.1574-6976.2008.00119.x","article-title":"Aminoacyl-tRNA synthetase complexes: Molecular multitasking revealed","volume":"32","author":"Hausmann","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"35063","DOI":"10.1074\/jbc.M006265200","article-title":"The Human Lysyl-tRNA Synthetase Gene Encodes Both the Cytoplasmic and Mitochondrial Enzymes by Means of an Unusual Alternative Splicing of the Primary Transcript","volume":"275","author":"Tolkunova","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ajhg.2013.05.018","article-title":"Mutations in KARS, Encoding Lysyl-tRNA Synthetase, Cause Autosomal-Recessive Nonsyndromic Hearing Impairment DFNB89","volume":"93","author":"Lee","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1111\/cge.12931","article-title":"Novel mutations in KARS cause hypertrophic cardiomyopathy and combined mitochondrial respiratory chain defect","volume":"91","author":"Verrigni","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/ejhg.2014.75","article-title":"6q22.1 microdeletion and susceptibility to pediatric epilepsy","volume":"23","author":"Szafranski","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00439-010-0934-0","article-title":"DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 16q21-q23.2","volume":"129","author":"Basit","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13023-018-0788-4","article-title":"KARS-related diseases: Progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature","volume":"13","author":"Ardissone","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e565","DOI":"10.1212\/NXG.0000000000000316","article-title":"Loss-of-function mutations in Lysyl-tRNA synthetase cause various leukoencephalopathy phenotypes","volume":"5","author":"Sun","year":"2019","journal-title":"Neurol. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1002\/humu.23799","article-title":"Mutations in KARS cause a severe neurological and neurosensory disease with optic neuropathy","volume":"40","author":"Scheidecker","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.ajhg.2010.09.008","article-title":"Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy","volume":"87","author":"McLaughlin","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1055\/s-0037-1598639","article-title":"Novel Causative Variants in DYRK1A, KARS, and KAT6A Associated with Intellectual Disability and Additional Phenotypic Features","volume":"6","author":"Murray","year":"2017","journal-title":"J. Pediatr. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jtho.2015.09.015","article-title":"Focused Analysis of Exome Sequencing Data for Rare Germline Mutations in Familial and Sporadic Lung Cancer","volume":"11","author":"Liu","year":"2016","journal-title":"J. Thorac. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/gim.2014.154","article-title":"Enhanced utility of family-centered diagnostic exome sequencing with inheritance model\u2013based analysis: Results from 500 unselected families with undiagnosed genetic conditions","volume":"17","author":"Farwell","year":"2015","journal-title":"Genet. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41436-018-0048-y","article-title":"Aminoacyl-tRNA synthetase deficiencies in search of common themes","volume":"21","author":"Fuchs","year":"2019","journal-title":"Genet Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/brain\/awz001","article-title":"Biallelic KARS pathogenic variants cause an early-onset progressive leukodystrophy","volume":"142","author":"Itoh","year":"2019","journal-title":"Brain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.ymgme.2015.01.006","article-title":"Case definition and classification of leukodystrophies and leukoencephalopathies","volume":"114","author":"Vanderver","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_22","first-page":"1225","article-title":"Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy","volume":"92","author":"Bugiani","year":"2019","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/ana.24650","article-title":"Whole exome sequencing in patients with white matter abnormalities","volume":"79","author":"Vanderver","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/acn3.50957","article-title":"Genome sequencing in persistently unsolved white matter disorders","volume":"7","author":"Helman","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1437\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:39:06Z","timestamp":1760179146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/11\/12\/1437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,29]]},"references-count":24,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["genes11121437"],"URL":"https:\/\/doi.org\/10.3390\/genes11121437","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,29]]}}}