Tang Miao, Sun Limei, Hu Andina, Yuan Miner, Yang Yu, Peng Xuening, Ding Xiaoyan
State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China.
Invest Ophthalmol Vis Sci. 2017 Nov 1;58(13):5949-5957. doi: 10.1167/iovs.17-22577.
LRP5, NDP, and TSPAN12 are known to be associated with familial exudative vitreoretinopathy (FEVR). In this study, a comprehensive mutation screening for the three genes was performed in patients with a clinical diagnosis of FEVR in Han Chinese.
Genomic DNA and clinical data were collected from 100 probands and their family members. Sanger sequencing was performed to screen for LRP5, NDP, and TSPAN12 mutations and phenotype-genotype correlation was analyzed.
There were 23 causative mutations identified in 23 unrelated probands (10/23 in LRP5, 8/23 in TSPAN12, and 5/23 in NDP). Apart from NDP mutations, only two LRP5 mutations inherited in an autosomal recessive manner. Among the 23 causative mutations, 13 were novel variants (4/10 in LRP5, 6/8 in TSPAN12, and 3/5 in NDP). According to the modified classification system, statistical significance was observed in the distribution of mutated genes (P = 0.049). None of the causative mutations was found in group I FEVR. Probands with LRP5 or NDP mutations were mainly categorized into group III and IV, TSPAN12 mutations were mainly observed in probands with group IV and V FEVR.
The detection rate for mutations in the three known genes was 23%. Mutations in LRP5 and TSPAN12 were more frequent, accounting for 10% and 8%, respectively. The NDP mutations were only identified in 6% in this cohort. There were 13 novel variants found, which provided a deeper understanding of this disease. Potential phenotype-genotype correlation was observed in the modified system. TSPAN12 mutations might lead to the most severe phenotype.
已知低密度脂蛋白受体相关蛋白5（LRP5）、诺里蛋白（NDP）和四跨膜蛋白12（TSPAN12）与家族性渗出性玻璃体视网膜病变（FEVR）有关。本研究对临床诊断为FEVR的汉族患者进行了这三个基因的全面突变筛查。
收集100名先证者及其家庭成员的基因组DNA和临床数据。采用桑格测序法筛查LRP5、NDP和TSPAN12突变，并分析表型-基因型相关性。
在23名无亲缘关系的先证者中鉴定出23个致病突变（LRP5中10/23，TSPAN12中8/23，NDP中5/23）。除NDP突变外，只有两个LRP5突变以常染色体隐性方式遗传。在这23个致病突变中，有13个是新变体（LRP5中4/10，TSPAN12中6/8，NDP中3/5）。根据改良分类系统，在突变基因的分布中观察到统计学意义（P = 0.049）。在I型FEVR组中未发现任何致病突变。LRP5或NDP突变的先证者主要归类为III组和IV组，TSPAN12突变主要见于IV组和V组FEVR先证者。
三个已知基因的突变检出率为23%。LRP5和TSPAN12突变更为常见，分别占10%和8%。在该队列中，NDP突变仅占6%。发现了13个新变体，这为深入了解该疾病提供了依据。在改良系统中观察到潜在的表型-基因型相关性。TSPAN12突变可能导致最严重的表型。
