Leber遗传性视神经病变线粒体ND6 T14502C突变的三个汉族家系

Leber＇s hereditary optic neuropathy is associated with the T14502C mutation in mitochondrial ND6 gene in three Han Chinese families

目的对3个中国汉族Leber遗传性视神经病变（LHON）家系的临床和分子遗传学特征进行分析。方法实验研究。收集3个临床诊断为LHON的中国汉族家系。对3个家系的先证者及母系成员进行眼科相关检查，并用24对部分重叠的引物进行全序列扩增。结果发现先证者视力轻度损害．家系外显率低，分别为：11．1％、10．O％、4．0％。3个家系的先证者都未携带NDlG3460A、ND4G11778A、ND6T14484C这3个常见原发突变，发现先证者的ND6T14502C（158V）同质性突变．多态性位点属于东亚线粒体单体型MlOa。mtDNAND614502位点T—C碱基的改变使ND6亚基第58位进化高度保守的异亮氨酸变为缬氨酸。结论线粒体ND6T14502C突变可能是LHON相关的线粒体突变位点之一。

Objective To report the clinical, genetic, and molecular characterizations of three Chinese families with Leber＇s hereditary optic neuropathy （LHON）. Methods Experimental study. Three Chinese Hart families were identified with LHON. Ophthahnologic examinations were conducted on the probands and other matrilineal relatives of these families. Meanwhile, entire nlitoehondrial DNA （mtDNA） of three probands were amplified by PCR using 24 pairs of oligonucleotiee primers with overlapping fragments. Results The probands had mild visual impairment. Strikingly, there was extremely low penetrance of visual impairment in these Chinese families, with a penetranee of 11.1%, 10.0% and 4.0%. Molecular analysis of mitochondrial DNA in these pedigrees revealed the absence of three common LHON associated with ND1 G3460A, ND4 Gl1778A, and ND6 T14484C mutations but there was a presence of homoplastic LHON associated with the ND6 T14502C （I58V） mutation in probands and other matrilineal relatives. These mtDNA polymorphism sites belong to the Asian haplogroups MlOa. The T14502C mutation in the ND6 gene, which is the substitution of a highly conserved isoleucine for valine （I58V） at the amino acid position 58, had changed the structure and influenced the function of protein, causing visual impairment. Conclusion The results suggest that the ND6 T14502C mutation might be involved in the pathogenesis of Leber＇s hereditary optic neuropathy in the three Chinese Hart families studied.