Abstract

Aim To obtain a whole genome-expression profile in Leber hereditary optic neuropathy (LHON), patients with the 11 778 mitochondrial DNA mutation.

Methods RNA was extracted from leucocytes and cDNA reverse-transcribed and hybridised to Affymetrix Gene Chips. A principal-component analysis and the rate monotonic algorithm were performed, and a further analysis applied to genes with a twofold expression difference and p<0.015 between patients and controls.

Results The gene-expression profile of patients with the 11 778 mtDNA mutation was significantly different from controls. The most commonly upregulated genes (n=137) were found to be related to the cellular transport (13.8%; 19/137) and transcription (12.4%; 17/137). Similarly, the most commonly downregulated genes (n=152) were also related to the cellular transport (17.8%; 27/152) and transcription (18.4%; 28/152). None of the 13 mitochondrial coded genes and no structural mitochondrial nuclear-encoded genes were differentially expressed. Interestingly, OPA1 gene was downregulated in all LHON patients, which could lead to fragmentation of the mitochondrial network, dissipation of the mitochondrial membrane potential and disorganisation of the cristae.

Conclusions The presence of the 11 778 mtDNA mutation resulted in a unique gene-expression profile compared with controls. Downregulation of OPA1 may contribute to the pathogenesis of LHON.