Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/180760
Title: | Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency |
Author: | Carreño-Gago, Lidia Juárez-Flores, Diana Luz Grau, Josep Maria Ramón, Javier Lozano Garcia, Ester Vila-Julià, Ferran Martí, Ramon Garrabou Tornos, Glòria Garcia-Arumí, Elena |
Keywords: | ADN mitocondrial Malalties del pàncrees Mitochondrial DNA Pancréas diseases |
Issue Date: | 5-Aug-2021 |
Publisher: | MDPI |
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 Gener ation 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 Mi tostress 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 nu cleotide change in exon 5 c.1391T>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 insuf ficiency, observed in both brothers, clinically considered as Pearson's syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson's syndrome characteristics and MLASA related phenotypes. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/jcm10163471 |
It is part of: | Journal of Clinical Medicine, 2021, vol. 10, num. 16, p. 3471 |
URI: | http://hdl.handle.net/2445/180760 |
Related resource: | https://doi.org/10.3390/jcm10163471 |
ISSN: | 2077-0383 |
Appears in Collections: | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
715013.pdf | 1.56 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License