中国人可疑遗传性视神经萎缩患者OPA1基因突变分析及临床特征  

Characteristics of OPA1 genotype in Chinese patients with suspected hereditary optic atrophy

作　　者：谢玥[1,2,3] 陈洁琼[1,2,3] 许可[1,2,3] 刘丽娟[1,2,3] 张晓慧[1,2,3] 蒋凤[1,2,3] 董冰[1,2,3] 李杨[1,2,3] 

机构地区：[1]首都医科大学附属北京同仁医院 [2]北京同仁眼科中心 [3]北京市眼科研究所 眼科学与视觉科学北京市重点实验室,100005

出　　处：《眼科》2015年第2期79-84,共6页Ophthalmology in China

基　　金：北京市卫生系统高层次卫生技术人才项目(2013-2-021);国家自然科学基金(81170878)

摘　　要：目的分析中国人常染色体显性遗传性视神经萎缩（ADOA）OPA1基因突变特点及ADOA患者临床特征。设计回顾性病例系列。研究对象北京同仁医院可疑ADOA患者291例，其中55例家族史明确，236例为散发患者。方法用PCR扩增DNA测序方法检测291例患者OPA1基因28个编码外显子，记录ADOA患者的临床特征。主要指标OPA1基因突变，家族史，发病年龄，视力，眼底表现。结果在291例患者中60例（20．6％）检测到51种OPA1基因致病突变，其中37种为本实验室新发现或首先报道的突变。基因突变中43％（22／51）为错义突变，19％（10／51）为无义突变，14％（7／51）为剪接位点突变，24％（12／51）为缺失或插入。OPA1基因突变主要分布于外显子27和9，频次分别为8和6次；其次为外显子8，26，28，频次均为5次。在60例ADOA患者中，6例（10％）携带相同缺失突变c．2708_2711delTTAG。ADOA患者中男女比例为1．4：1，发病年龄（7．97±7.31）岁（范围3～33岁），女性患者发病年龄小于男性。平均logMAR视力（0．84±0．42）。60例患者均双眼同时发病，眼底表现对称，45例（75％）表现为双眼视盘颞侧色淡，13例（22％）表现为双眼全视盘色淡。结论本研究结果扩大了OPA1基因突变谱，外显子8，9，26．28是ADOA患者OPAl基因突变的热突变区域，对可疑ADOA患者应进行OPA1基因测序。Objective To report the results of mutation analysis of the OPA1 gene in a cohort of patients with suspected hereditary optic atrophy and describe clinical features of autosomal dominant optic atrophy （ADOA） patients. Design Retrospective case series. Participants Two hundred and ninety-one suspected ADOA probands who have been excluded from 16 primary mitochondrial DNA mutations associated with Leber hereditary optic neuropathy （LHON） in our prior screening. Among them 55 had a family history of hereditary optic neuropathy, and 236 were sporadic cases. All patients were unrelated. Methods The coding region （exon 1-28）, including intron-exon boundary of the OPA1 gene, were screened in participants and some family members by using PCR-based sequencing methods. The clinical features of ADOA patients were recorded. Main Outcome Measures Mutations of OPAl gene, family history, age of onset, visual acuity, and fundus photography. Results Fifty-one OPAl pathogenic mutations were found in 60 patients （60/291, 20.6%）. Of the 51 intragenic mutations, 37 were detected for the first time in this study or in our precious studies. The mutations contained 43 % （22/51） of missense mutations, 19% （10/51） o f nonsense mutations, 14% （7/51） of splice site mutations, and 24% （12/51） of deletions or insertions. The majority of OPAl intragenic mutations were located in exon 27 and 9, for 8 and 6 times, respectively. Followed by exon 8, 26 and 28, where mutations had been identified 5 times. One reported mutation c.2708_2711 delTTAG in exon 27 was identified in 6 unrelated probands. The male-to-female ratio of the 60 positive probands was almost 1.4：1. The mean onset age of visual deficit was 7.97±7.31 years （ranging from 3-33 years） and the mean logMAR visual acuity for the probands carrying OPA1 mutations was 0.84±0.42. Sixty ADOA patients presented with bilateral, symmetric visual failure and optic nerve degeneration. In this study, the appearance of the optic nerve head was divided into two

关 键 词：常染色体显性遗传性视神经萎缩 OPA1基因突变 

分 类 号：R774.63[医药卫生—眼科]