Leber遗传性视神经病变11778突变家系异质性的研究

目的研究Leber遗传性视神经病变（LHON）11778点突变家系的异质性，分析异质性对LHON的发病率和患者视力的影响。方法研究5个11778点突变LHON家系，其中母系成员68例，发病者27例；除2例携带者外，66例母系成员接受检查。应用聚合酶链式反应、限制性核酸内切酶酶切、变性高效液相色谱分析等技术，分析家系之间突变的异质性以及异质性与发病和视力预后的关系。结果在5个家系中，2个家系为同质突变（纯合突变），包括24例母系成员和10例患者；3个家系为异质突变（杂合突变），包括42例母系成员和17例患者。同质突变和异质突变母系成员之间LHON的发病率比较，差异无统计学意义；2种突变患者之间的视力比较，差异亦无统计学意义。结论LHON患者11778的突变存在异质性，但其异质性对发病和视力预后均无影响。

Heteroplasmy of Leber's hereditary optic neuropathy families with 11778 mutation

Objective Leber＇ s hereditary optic neuropathy （LHON） is a maternally inherited blindness occurring predominantly in young adult males. The disease is typically characterized by acute or subacute visual loss, and penetrance vary among different pedigrees and even members in the same family. The geue mutation,other factors such as secondary gene,level of mtDNA mutation and/or environment also are associated with the development of the disease. This study was to investigate the heteroplasmy of 11778 mutation families in LHON and analyse its influence on prevalence and vision. Methods Five families of LHON with 11778 mutations, including 68 maternal members and 27 affected patients, were studied, in which 66 maternal members with symptom were examined. Polymerase chain reaction （PCR） , restriction endonuclease digestion, denaturing high performance liquid chromatography（dHPLC） were used to study the heteroplasmy in the maternal members, and the correlations between heteroplasmy and prevalence or vision were analysed. Results In the 5 families, 2 families were homoplasmic mutation,including 24 maternal members and 10 patients,and 3 families were heteroplasmy which included 42 maternal members and 17 patients. No statistical difference was found in the prevalence between heteroplasmic and bomoplasmic material members （X^2 = 0. 159, P = 0. 690）. No significant difference was detected in the IogMAR vision between the heteroplasmic and homoplasmic patients（ t = 0. 543, P = 0.59）. Conclusion Heteroplasy in LHON with 11778 mutation does not influent the prevalence and the prognosis of vision.