Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency
Carreño Gago, Lidia (Vall d'Hebron Institut de Recerca (VHIR))
Juarez-Flores, Diana Luz (Hospital Clínic i Provincial de Barcelona)
Grau, Josep Maria (Universitat de Barcelona)
Ramón, Javier (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Lozano, Ester (Universitat de Barcelona)
Vila-Julià, Ferran (Vall d'Hebron Institut de Recerca (VHIR))
Martí, Ramon A. (Vall d'Hebron Institut de Recerca (VHIR))
Garrabou, Glòria (Universitat de Barcelona)
García Arumí, Elena (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI15/01428 Ministerio de Economía y Competitividad PMP15/00025 Instituto de Salud Carlos III PI18/00498 Instituto de Salud Carlos III PI19/01772
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Mitochondrial aminocyl-tRNA synthetase ; Novel pathogenic variant ; Pearson's syndrome
Published in:	Journal of clinical medicine, Vol. 10 (august 2021) , ISSN 2077-0383

DOI: 10.3390/jcm10163471
PMID: 34441767

12 p, 1.5 MB

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