中国人Leber遗传性视神经病变线粒体DNA突变频谱

Spectrum of pathologic mitochondria DNA mutations in Chinese patients with Leber′s hereditary optic neuropathy

目的 分析中国人 L eber遗传性视神经病变 (L eber′s hereditary optic neuropathy,L HON)线粒体 DNA(mitochondrial DNA ,mt DNA) 3个原发致病基因突变的频谱及其遗传特征。 方法 分别用突变特异性引物聚合酶链反应 (mutation- specific priming polymerase chain reaction,MSP- PCR)、异源双链 -单链构象多态性 (heteroduplex- single strand conformation polymorphism polymerase chain reaction,HA- SSCP)、限制性片段长度多态性 (restriction fragmentlength polymorphisms,RFL P)和 DNA测序等方法 ,对 14 0个 L HON家系的先证者 (男 12 0人 ,女 2 0人 )进行 mt DNA3个原发致病突变位点 ,即 G11778A、G346 0 A和 T14 4 84 C的检测 ,并对这些患者的家系进行遗传分析。 结果 在 14 0例 L HON先证者中 ,130例 (男 113人 ,女 17人 )为 G11778A位点突变 ,占 92 .9% ;2例 (男、女各 1人 )为 G346 0 A位点突变 ,占1.4 % ;8例 (男 6人 ,女 2人 )为 T14 4 84 C位点突变 ,占 5 .7%。 结论 中国人 L HON患者 mt DNA3个原发致病突变中 ,以 G11778A位点突变为主 ,少数为 G346 0 A和 T14 4 84 C位点的突变。

Objective To investigate the spectrum of mitochondrial DNA (mtDNA) mutations in Chinese patients with Leber′s hereditary optic neuropathy (LHON). Methods The primary mtDNA mutations (G3460A?G11778A and T14484C) of 140 patients with LHON were detected by mutation-specific priming polymerase chain reaction (MSP-PCR), heteroduplex-single strand conformation polymorphism polymerase chain reaction (HA-SSCP), restriction fragment length polymorphisms (RFLP) and measurement of DNA sequence. The transmissibility of the patients′ stirps was analyzed. Results In the 140 patients with LHON, G11778A mtDNA primary mutation was found in 130 (92.9%), including 113 males and 17 females; G3460A mutation was found in 2 (1.4%) including 1 male and 1 female; G14484A mutation was found in 8 (5.7%) including 6 males and 2 females. Conclusion In Chinese patients with LHON, the incidence of G11778A mtDNA mutation is higher than that of G3460A and T14484C.