 Hi, I'm Arno Van Ande and I'm glad to introduce you to our new paper recently published in Human Mutation entitled Two Siblings with a homozygous pathogenic spliceid variant in the mitochondrial asparaginial tRNA synthetase. My name is Rudy van Koster and I am working at the University Hospital in Canada, Belgium. We are a small mitochondrial research unit active in the diagnosis of patients suspected of having a mitochondrial defect. During more than two decades now, we are performing diagnostic tests. And during that period, we have collected almost 30 patients with a combined efficiency of complex one and four of the oxidative asphylation. In this cohort of patients, the mitochondrial DNA was thoroughly searched. We suspected that this type of combined oxfoss deficiency was due to the defect in a nuclear gene coding for a protein necessary for mitochondrial replication, transcription or translation. In Two Siblings, we detected a new gene effect located in ours too, the gene that codes for the mitochondrial asparaginial tRNA synthetase. We collaborated with Pierre Manton from the Medical Genetic Department at our hospital. And to prove the pathogenicity of the nucleotide variation in the gene, we collaborated with Michael Minczuk from Cambridge specialized in a specific area of mitochondrial research. It is not the first time that we have found a new gene effect. Until now, we have detected five new gene effects. The first was located in the glycosidease 1, then ATP12, in aminoacyase 1, IBA57 and now in NARS2. Now it is time for my collaborators to show how we have detected the NARS2 defect in the Two Siblings. The last decade, the research field on oxfoss deficiencies has broken the scope by including the nuclear genome in the search for molecular causes of diseases. Indeed, the whole necessary machinery for mitochondrial protein translation is included by this nuclear genome. One group of enzymes taking part in the almost magical transformation of the genetic codes into proteins are the aminoacyl tRNA synthetases. As you can see on this little animation, the enzyme links a particular amino acid to his dedicated tRNA using ATP. The charged tRNA is then released, ready to add his amino acid on the growing polypeptide chain on the ribosome. In the current study, we identified two patients with a remarkable oxfoss deficiency, indicative of a translation deficiency. Considering their consanguinous descent, we used homozygosity mapping together with whole exo sequencing to try to identify the culprit gene. By these means, we identified a pathogenic variant in the gene encoding the asparaginil aminoacyl tRNA synthetase. Considering the position of the identified variant, which was at the entrant-exon boundary, we wondered if this could influence the splicing of this gene. For these reasons, we performed sequencing of the cDNA and indeed confirmed that the variant influenced splicing. This reinforces the pathogenic character of the variant. At that time, we contacted our colleagues from Cambridge who could demonstrate in lymphoblast isolated from one of our patients that the charging of the tRNA for asparaginil was faulty. Finally, using Western blotting, we could confirm lower abundance of the NARS-2 protein in patient tissue. I hope you enjoyed our presentation and for more details, we refer to our paper in Human Mutation. Thank you.