Identification of a novel OXCT1 frameshift mutation by whole-exome sequencing and evidence for nonsense-mediated mRNA decay

Background: Autosomal recessive disorders are the most common forms of hereditary diseases in consanguineous populations. Despite their frequencies, the diagnosis of these disorders continues to be a challenging task, given their extreme genetic heterogeneities. However, since the discovery of next-generation sequencing-based techniques, the number of pathogenic mutations linked to autosomal recessive disorders has increased dramatically due to the time and cost-effectiveness of these methods. Succinyl-CoA: 3-ketoacid CoA transferase (SCOT) deficiency is considered as one of these rare autosomal recessive genetic disorders. Aim and Objectives: In the present study, we aimed to identify the responsible mutation in a UAE family with autosomal recessive SCOT deficiency. Materials and Methods: Whole-exome sequencing was performed in the affected individual. Sanger sequencing was used to confirm the existence and the segregation of the novel pathogenic mutation. Real-time polymerase chain reaction (PCR) was used to measure the expression of the OXCT1 gene in the mRNA of affected, carrier and normal individuals. Results: Our analysis revealed a new frameshift mutation. Sanger sequencing confirmed its homozygosity in the patient and its cosegregation with the disease in the studied family. Using real-time PCR, we showed that this new frameshift mutation affects the OXCT1-mRNA by nonsense-mediated mRNA decay (NMD). Conclusion: To the best of our knowledge, this is the first study associating SCOT deficiency with an OXCT1 frameshift mutation in the world. In addition, we report for the first time by studying this new OXCT1 mutation evidence for an NMD effect associated with SCOT mutations.