遗传性Leber视神经病变家系致病基因突变分析

目的 探讨遗传性Leber视神经病变(LHON)家系的致病基因突变位点.方法 家系调查研究.对LHON家系成员进行临床检查,抽取部分家系成员外周血提取基因组DNA,应用聚合酶链反应(PCR)和DNA序列测定法,检测家系成员线粒体DNA上的突变位点.结果 该家系3代14例成员中共有7例患者,其中男性2例,女性5例,家系图分析符合母系遗传特征.对其中4例患者及3例未发病家系成员进行线粒体DNA突变检测,显示4例患者及2例未发病家系成员携带G11778A位点突变.结论 线粒体DNA的G11778A突变位点是导致该家系患者发病的致病基因.对尚未发病的基因突变携带者进行早期干预治疗,有可能延缓或阻止疾病的发生与发展.

Mutation analysis in a family of Leber hereditary optic neuropathy

Objective To identify the disease-causing mutation in a family of Leber hereditary optic neuropathy (LHON). Methods Clinical data and family information were collected. Peripheral venous blood was drawn from patients and family members who agreed to donate the blood samples.Genomic DNA was extracted from blood leukocytes.Three primary mitochondrial DNA (mtDNA) mutations,G3460A,G11778A,and T14484C were screened using a method of polymerase chain reaction (PCR) followed by direct sequencing. Results This 3-generation family had 14 members. Seven family members were affected,including 5 female patients and 2 male patients.Pedigree analysis showed maternal inheritance.Mutation analysis in 4 affected and 3 unaffected family members showed G11778A mutation in all 4 affected and 2 of the 3 unaffected individuals.Conclusions G11778A mutation in mtDNA is the disease-causing mutation in this family of LHON.For the mutation carriers,early intervention may prevent or delay the onset of the disease.