Johns D R, Neufeld M J, Park R D
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21287-7619.
Biochem Biophys Res Commun. 1992 Sep 30;187(3):1551-7. doi: 10.1016/0006-291x(92)90479-5.
A mitochondrial DNA mutation at nucleotide position 14,484 was found in 14 independent probands with Leber hereditary optic neuropathy and in 0/250 controls. The 14,484 mutation, which changes methionine-64 to valine in a conserved domain of the ND-6 gene, occurred in association with a mitochondrial DNA haplotype that includes the 13,708 secondary mutation in 10/14 probands. An associated mutation at nucleotide position 3,394, which changes conserved tyrosine-30 to histidine in the ND-1 gene, was observed in 5/14 probands positive for the 14,484 mutation, all of whom harbored the same mitochondrial DNA haplotype. Multiple mitochondrial DNA mutations may interact in the pathogenesis of Leber hereditary optic neuropathy and the 13,708 secondary mutation appears to play a central role in this process.
在14例独立的Leber遗传性视神经病变先证者中发现了核苷酸位置14484处的线粒体DNA突变，而在250名对照中未发现该突变。14484突变导致ND-6基因保守结构域中的甲硫氨酸-64变为缬氨酸，在10/14的先证者中，该突变与包含13708二次突变的线粒体DNA单倍型相关。在14例14484突变阳性的先证者中，有5例观察到核苷酸位置3394处的相关突变，该突变导致ND-1基因中保守的酪氨酸-30变为组氨酸，所有这些先证者都具有相同的线粒体DNA单倍型。多个线粒体DNA突变可能在Leber遗传性视神经病变的发病机制中相互作用，而13708二次突变似乎在这一过程中起核心作用。
