Novel CNGA3 mutations in Chinese patients with achromatopsia
Novel CNGA3 mutations in Chinese patients with achromatopsia
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中国色盲患者中出现新的 CNGA3 突变
DOI：
10.1136/bjophthalmol-2014-305432
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发表时间：
2015-04-01
影响因子：
4.1
通讯作者：
Sui, Ruifang
中科院分区：
文献类型：
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作者：
Liang, Xiaofang;Dong, Fangtian;Sui, Ruifang
目的探讨中国色盲（ACHM）患者的临床特点及致病性突变。设计本研究纳入来自10个无血缘关系家庭的15例患者。对受影响的受试者进行详细的眼部检查，包括最佳矫正视力（BCVA）、色觉、裂隙灯、眼底、视网膜电图、视野检查和光谱域光学相干地形图（SD-OCT）。采集所有患者及其家庭成员外周血，提取基因组DNA。通过PCR扩增CNGA3、CNGB3、GNAT2、PDE6C和PDE6H的所有外显子，并通过直接Sanger测序筛选突变。利用Blat工具对序列进行分析，然后与基因转录本进行比较。如果病人的父母可以的话，对他们进行了隔离测试。将这些变异与千人基因组计划数据库进行比较，以排除多态性。结果所有患者均有眼球震颤、畏光、辨色障碍。受影响受试者的BCVA范围为0.05-0.2。观察到严重抑郁和不可记录的视锥电图。SD-OCT观察到明显的结构变化，包括黄斑内/外节（IS/OS）连接的破坏或丢失。在来自8个家族的13例患者中发现了CNGA3突变。测序显示这些患者中有7个新的错义突变，3个新的缺失突变和4个先前报道的突变。结论CNGA3突变是本组患者发生ACHM的最常见原因。在CNGA3中发现了10个新的突变。ACHM患者的遗传特征对遗传咨询和未来的基因治疗很重要。本研究报道了中国ACHM患者的综合临床和遗传特征。
Objective To study the clinical features and to identify the pathogenic mutations in Chinese patients with achromatopsia (ACHM). Design Fifteen patients from 10 unrelated families were included in this study. Detailed ocular examinations were performed for the affected subjects, including best-corrected visual acuity (BCVA), colour vision, slit lamp, fundus, electroretinography, perimetry, and spectral domain optical coherent topography (SD-OCT). Peripheral blood samples were obtained from all of the patients and their family members for genomic DNA extraction. All exons of CNGA3, CNGB3, GNAT2, PDE6C and PDE6H were amplified by a PCR and screened for mutation by direct Sanger sequencing. The sequences were analysed using the Blat tool and then compared with the gene transcript. A segregation test was conducted in the patients’ parents if they were available. The variants were compared with the database of the 1000 Genomes Project to exclude polymorphism. Results Nystagmus, photophobia, and impaired colour discrimination were observed in all patients. The BCVA of the affected subjects ranged from 0.05–0.2. Severely depressed and non-recordable cone electroretinograms were observed. Noticeable structural changes including disruption or loss of the macular inner/outer segments (IS/OS) junction of the photoreceptors were observed with SD-OCT. CNGA3 mutations were identified in 13 patients from eight families. Sequencing revealed seven novel missense mutations, three novel deletion mutations, and four previously reported mutations among those patients. Conclusions CNGA3 mutation is the most frequent cause of ACHM in this cohort of patients. Ten novel mutations were identified in CNGA3. Genetic characterisation of patients with ACHM is important for genetic counselling and future gene therapies. This study reports the comprehensive clinical and genetic features of Chinese patients with ACHM.