中华眼底病杂志

中华眼底病杂志

Usher综合征2型一家系USH2A基因新突变

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目的定位1个Usher综合征2型(USH2)家系的致病基因突变。方法1个USH2家系3代7名成员纳入研究。其中,患者2例、健康成员5名。2例患者均为男性。所有受试者均行最佳矫正视力、裂隙灯显微镜、间接检眼镜、全视野视网膜电图、光相干断层扫描、视野检查。采集所有受试者外周静脉血3 ml,提取基因组DNA。选择136个遗传性视网膜疾病致病基因作为目标基因;将提取的DNA采用高通量测序并与数据库对比,确定候选致病基因突变位点。聚合酶链反应和直接测序法在家系成员及100名正常对照者中进行验证,确定致病性突变位点。结果DNA测序发现,2例患者均携带USH2A基因第27号外显子c.5459T>C(p.M1820T)、第7号外显子c.1190T>A(p.I397K)、第5号外显子c.802G>A(p.G268R)3个杂合性错义突变,其中c.5459T>C和c.1190T>A为新发现突变。患者表型正常的父亲、母亲分别为c.1190T>A(p.I397K)错义突变携带者和c.5459T>C(p.M1820T)和c.802G>A(p.G268R)复合杂合突变携带者。根据基因检测结果表明该家系的遗传方式为常染色体隐性遗传。其余表型正常的家系成员和正常对照者均未同时检测到这3个突变位点。突变在该家系中呈现共分离状态。结论USH2A基因杂合性错义突变c.5459T>C(p.M1820T)、c.1190T>A(p.I397K)、c.802G>A(p.G268R)是该家系的致病基因。

ObjectiveTo identify the pathogenic genes and mutations in a family with Usher syndrome type 2.MethodsA three-generation family including 7 individuals was enrolled in this study. There were 2 male patients and 5 unaffected individuals. All participants was underwent related ophthalmologic examination, including best corrected visual acuity, slit-lamp, indirect ophthalmoscopy, electroretinogram (ERG), optical coherence tomography and visual field test. DNA was extracted from 3 ml peripheral venous blood of all participants. A total of 136 hereditary retinal disease target genes were screened and the DNA sequence was performed by Next-generation sequence analysis. Then the suspected mutations compared with databases to identify the suspected mutations, which should be verified with non-affected family members and 100 normal subjects by PCR and Sanger sequence.ResultsThe sequence result showed that 2 patients, the proband and his brother, carried complex heterozygous mutations in the USH2A gene: c.5459T>C (p.M1820T) in exon 27, c.802G>A (p.G268R) in exon 5 and c.1190T>A (p.I397K) in exon 7. The c.5459T>C and c.1190T>A mutations in USH2A have not been reported in the literature and database. Although their mother carried c.5459T>C (p.M1820T) and c.802G>A (p.G268R), and their father carried c.1190T>A (p.I397K) heterozygous mutations, the parents did not present phenotype. These mutations were not detected in other normal family members. The result was supported by co-segregation analysis.ConclusionThe heterozygous mutations c.5459T>C (p.M1820T), c.1190T>A (p.I397K) and c.802G>A (p.G268R) in USH2A gene cause Usher syndrome in this family.

关键词: Usher综合征/遗传学; Usher综合征/病因学; 基因; 突变; 序列分析

Key words: Usher syndromes/genetics; Usher syndromes/etiology; Genes; Mutation; Sequence analysis

引用本文: 程萌, 杨鸽, 雷博, 刘宇莹, 金学民. Usher综合征2型一家系USH2A基因新突变. 中华眼底病杂志, 2018, 34(3): 268-271. doi: 10.3760/cma.j.issn.1005-1015.2018.03.014 复制

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