Johns D R, Neufeld M J
Department of Neurology, Beth Israel Hospital, Harvard Medical School, Boston, MA 02115.
Biochem Biophys Res Commun. 1993 Oct 29;196(2):810-5. doi: 10.1006/bbrc.1993.2321.
New mitochondrial DNA mutations were discovered in the cytochrome c oxidase subunit III gene in 8 independent Leber hereditary optic neuropathy probands. A mutation at nucleotide position 9438 was found in 5 probands, changed highly conserved glycine-78 to serine (G78S), and was not found in controls. A mutation at nucleotide position 9804 was found in 3 probands, changed highly conserved alanine-200 to threonine (A200T), and also was not found in controls. The 9438 mutation is readily detected by the loss of a Stu 1 restriction site and the 9804 mutation is detected by the gain of an Mae III restriction site. These mtDNA mutations may represent the first convincing examples of cytochrome c oxidase (Complex IV) mutations associated with a human disease.
在8个独立的Leber遗传性视神经病变先证者中，发现细胞色素c氧化酶亚基III基因存在新的线粒体DNA突变。在5个先证者中发现核苷酸位置9438处的突变，将高度保守的甘氨酸-78变为丝氨酸（G78S），而在对照中未发现该突变。在3个先证者中发现核苷酸位置9804处的突变，将高度保守的丙氨酸-200变为苏氨酸（A200T），同样在对照中未发现该突变。9438突变可通过Stu 1限制性酶切位点的缺失轻易检测到，9804突变可通过Mae III限制性酶切位点的获得检测到。这些线粒体DNA突变可能是与人类疾病相关的细胞色素c氧化酶（复合体IV）突变的首个有说服力的例子。
