Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of the splice variants

The effect on the stability of alternative transcripts of different mutations of the NDUFS4 gene in patients with Leigh syndrome with complex I deficiency is presented. Normally, two NDUFS4 splice variants are degraded by nonsense mediated mRNA decay (NMD) while a third form does not trigger NMD degradation. In a patient with a premature termination codon in exon 1, all the three splice variants are up-regulated. The present is the first case of a nonsense mutation leading to the abrogation of NMD, which can represent an additional event to be considered in the evaluation of clinically relevant mutations.