{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:38Z","timestamp":1785183878023,"version":"3.55.0"},"reference-count":29,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T00:00:00Z","timestamp":1628121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/01428"],"award-info":[{"award-number":["PI15\/01428"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PMP15\/00025"],"award-info":[{"award-number":["PMP15\/00025"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00498"],"award-info":[{"award-number":["PI18\/00498"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/01772"],"award-info":[{"award-number":["PI19\/01772"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA replication were studied by Next Generation Sequencing (NGS) and whole exome sequence with the TruSeq Rapid Exome kit (Illumina, San Diego, CA, USA). Mitochondrial protein translation was studied following the Sasarman and Shoubridge protocol and oxygen consumption rates with Agilent Seahorse XF24 Analyzer Mitostress Test, (Agilent, Santa Clara, CA, USA). We report two siblings with two novel compound heterozygous pathogenic variants in YARS2 gene: a single nucleotide deletion in exon 1, c.314delG (p.(Gly105Alafs*4)), which creates a premature stop codon in the amino acid 109, and a single nucleotide change in exon 5 c.1391T&gt;C (p.(Ile464Thr)), that cause a missense variant in amino acid 464. We demonstrate the pathogenicity of these new variants associated with reduced YARS2 mRNA transcript, reduced mitochondrial protein translation and dysfunctional organelle function. These pathogenic variants are responsible for late onset MLASA, herein accompanied by pancreatic insufficiency, observed in both brothers, clinically considered as Pearson\u2019s syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson\u2019s syndrome characteristics and MLASA related phenotypes.<\/jats:p>","DOI":"10.3390\/jcm10163471","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T21:43:53Z","timestamp":1628199833000},"page":"3471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency"],"prefix":"10.3390","volume":"10","author":[{"given":"Lidia","family":"Carre\u00f1o-Gago","sequence":"first","affiliation":[{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, Vall d\u2019Hebron Institut de Recerca (VHIR), Vall d\u2019Hebron Hospital Universitari, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Luz","family":"Ju\u00e1rez-Flores","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Science-University of Barcelona, Internal Medicine Service-Hospital Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep Maria","family":"Grau","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"},{"name":"Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine and Health Science-University of Barcelona, Internal Medicine Service-Hospital Cl\u00ednic of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-9338","authenticated-orcid":false,"given":"Javier","family":"Ram\u00f3n","sequence":"additional","affiliation":[{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, Vall d\u2019Hebron Institut de Recerca (VHIR), Vall d\u2019Hebron Hospital Universitari, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6307-9807","authenticated-orcid":false,"given":"Ester","family":"Lozano","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Vila-Juli\u00e0","sequence":"additional","affiliation":[{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, Vall d\u2019Hebron Institut de Recerca (VHIR), Vall d\u2019Hebron Hospital Universitari, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-9540","authenticated-orcid":false,"given":"Ramon","family":"Mart\u00ed","sequence":"additional","affiliation":[{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, Vall d\u2019Hebron Institut de Recerca (VHIR), Vall d\u2019Hebron Hospital Universitari, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n 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