A whole mitochondrial genome screening in a MELAS patient: A novel mitochondrial tRNAVal mutation

► We report a young Tunisian patient with clinical features of MELAS syndrome. ► Reported mitochondrial mutations were absent after a mutational screening of the whole mtDNA. ► We described a novel m.1640A>G mutation in the tRNAVal gene which was absent in 150 controls. ► Mitochondrial deletions and POLG1 gene mutations were absent. ► The m.1640A>G mutation could be associated to MELAS syndrome. Mitochondrial encephalopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a mitochondrial disorder characterized by a wide variety of clinical presentations and a multisystemic organ involvement. In this study, we report a Tunisian girl with clinical features of MELAS syndrome who was negative for the common m.3243A>G mutation, but also for the reported mitochondrial DNA (mtDNA) mutations and deletions. Screening of the entire mtDNA genome showed several known mitochondrial variants besides to a novel transition m.1640A>G affecting a wobble adenine in the anticodon stem region of the tRNAVal. This nucleotide was conserved and it was absent in 150 controls suggesting its pathogenicity. In addition, no mutations were found in the nuclear polymerase gamma-1 gene (POLG1). These results suggest further investigation nuclear genes encoding proteins responsible for stability and structural components of the mtDNA or to the oxidative phosphorylation machinery to explain the phenotypic variability in the studied family.