Leber’s遗传性视神经病变一个双生子家系的研究

Clinical and molecular genetic researches of a family with Leber's hereditary optic neuropathy

目的探讨Leber’s遗传性视神经病变(Leber’shereditaryopticneuropathy,LHON)一个双生子家系的临床和分子遗传学特征。方法对LHON一个家系进行家系调查,分析其遗传特征和发病特点,并对家系成员(发病者、未发病者及对照者)进行眼科临床检查(包括视力、视野、眼底及电生理检查)和线粒体基因三个原发性突变位点的检测,即自全血提取线粒体DNA(mtDNA),应用聚合酶链反应技术,分别扩增mtDNA上相应片段检测G3460A、G11778A和T14484C位点突变。最后应用分子遗传学技术对该家系中的一对双生子(其中一人为先证者,另一个未患病)进行DNA多态性的比较分析以鉴定其卵性。结果该家系显示为典型的母系遗传,先证者的临床表现为典型的LHON患者表现;母系亲属mtDNA的G11778A位点突变阳性,G3460A和T14484C位点突变阴性,而对照者三个位点检测结果均为阴性,双生子卵性鉴定结果为异卵双生。结论该家系为典型的LHON家系,mtDNA上G11778A位点突变可导致LHON的发生,但并不是所有G11778A位点突变者均发生LHON。

Objective To inviolate, the characterization of a four-generation large family with Leber＇s hereditary optic neuropathy （LHON）. Methods The ophthalmological examinations of proband and other members of this family and controls were. conducted, and Genomic DNA was isolated from whole blood of participants. Their DNA fragments were FCR-amplified using oligedeoxynuclcotides corresponding to mtDNA at positions 3108 - 3717 for the G3460A mutation, 11,654- 11,86.5 for the. G11778A mutation, and 14,260- 14,510 for the T14484C mutation, respectively. For the detection of the three primazy mutations, testing of the gene sequence were performed on the amplified PCR segments. And molecular genetic analysis was performed on DNA extracted from the twins Ⅳ-3 and Ⅳ-4 to identify whether they are monozygotc twins（MZ） or dizygetic twins（DZ）. Results The family history was consistent with a maternal inberitance and the proband exhibited a typical clinical feature of LHON. Molecular analysis identified the presence of the G11778A mutation, The twins Ⅳ-3, who was the proband, and Ⅳ-4 were dizygetic twins（DZ）. Conclusion The family exhibited a typical LHON family clinically. It is the G11778A point mutation that leads to the presence of LHON in this large Chinese family. However, not all family members with the presence of the G11778A point mutation are inevitably suffered from LHON.