Rao Feng-Qin, Cai Xue-Bi, Cheng Fei-Fei, Cheng Wan, Fang Xiao-Long, Li Na, Huang Xiu-Feng, Li Li-Hong, Jin Zi-Bing
Division of Ophthalmic Genetics, Lab for Stem Cell & Retinal Regeneration, Institute of Stem Cell Research, The Eye Hospital, Wenzhou Medical University, State Key Laboratory of Ophthalmology, Optometry and Vision Science, Wenzhou, China.
Maternal and Children's Hospital, Kunming, Yunnan, China.
Invest Ophthalmol Vis Sci. 2017 May 1;58(5):2623-2629. doi: 10.1167/iovs.16-21324.
Familial exudative vitreoretinopathy (FEVR) is a severe hereditary retinal disorder characterized by defects in retinal vascular development. To date, six genes have been reported to be responsible for this disease, including LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to investigate the genetic defects in Chinese patients with FEVR through mutational analyses of 31 pedigrees.
Clinical data and peripheral blood were collected from 31 pedigrees with FEVR. All coding sequences and intron/exon junctions were amplified and sequenced comprehensively, followed by cosegregation testing to verify suspected variants in the family members. Finally, we assessed clinical relevance of the identified mutations, according to the standards and guidelines from the American College of Medical Genetics and Genomics.
Twelve index cases (12/31, 38.7%) were confirmed to harbor mutations in the known genes, including one previously reported mutation and 11 novel mutations. Among the detected mutations, LRP5 accounted for the largest proportion with a mean mutation rate of 16.1% (5/31, 16.1%), followed by NDP (3/31, 9.7%), FZD4 (2/31, 6.5%), TSPAN12 (1/31, 3.2%), and KIF11 (1/31, 3.2%). All the novel changes were predicted to be pathogenic by a series of bioinformatics analyses.
We comprehensively screened six known disease-causing genes in 31 pedigrees with FEVR and achieved a clear picture of the mutation spectrum in Chinese patients with FEVR, which highlights the importance and utility of clinical genetic diagnosis.
家族性渗出性玻璃体视网膜病变（FEVR）是一种严重的遗传性视网膜疾病，其特征为视网膜血管发育缺陷。迄今为止，已有六个基因被报道与该疾病相关，包括LRP5、FZD4、TSPAN12、NDP、ZNF408和KIF11。我们研究的目的是通过对31个家系进行突变分析，来探究中国FEVR患者的基因缺陷。
收集了31个FEVR家系的临床资料和外周血。对所有编码序列和内含子/外显子连接区进行全面扩增和测序，随后进行共分离检测以验证家族成员中疑似的变异。最后，我们根据美国医学遗传学与基因组学学会的标准和指南，评估所鉴定突变的临床相关性。
12例先证者（12/31，38.7%）被证实携带已知基因的突变，其中包括1个先前报道的突变和11个新突变。在检测到的突变中，LRP5占比最大，平均突变率为16.1%（5/31，16.1%），其次是NDP（3/31，9.7%）、FZD4（2/31，6.5%）、TSPAN12（1/31，3.2%）和KIF11（1/31，3.2%）。通过一系列生物信息学分析，所有新发现的变异均被预测为致病性的。
我们对31个FEVR家系中的六个已知致病基因进行了全面筛查，明确了中国FEVR患者的突变谱，这突出了临床基因诊断的重要性和实用性。
