OBJECTIVETo investigate the role of MT-ND1 m.3635G>A mutation in the pathogenesis of Leber's hereditary optic neuropathy (LHON).

METHODSBiochemical characteristics including the activity of complex Ⅰ, ATP production and oxygen consumption rate among lymphoblastoid cell lines derived from 3 carriers, 3 affected matrilineal relatives of the families and 3 controls were compared.

RESULTSComparison of mitochondrial functions in lymphoblastoid cell lines of the carriers, patients and controls showed a 51.0% decrease in the activity of complex Ⅰ in patients compared with controls (P<0.05). The m.3635G>A mutation has resulted in decreased efficiency of ATP synthesis (P<0.05). Comparison of oxygen consumption rate showed that the basal OCR (P<0.05), ATP-linked OCR (P<0.05) and the maximum OCR (P<0.05) have all reduced to some extent compared with the controls.

CONCLUSIONThese results showed that m.3635G>A, as a LHON-associated mutation, can lead to mitochondrial dysfunction.

Adenosine Triphosphate ; genetics ; Asian Continental Ancestry Group ; genetics ; Female ; Humans ; Male ; Mitochondria ; genetics ; Mutation ; genetics ; NADH Dehydrogenase ; genetics ; Optic Atrophy, Hereditary, Leber ; genetics ; Pedigree