Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
Genet Test Mol Biomarkers. 2021 Jun;25(6):399-404. doi: 10.1089/gtmb.2021.0019. Epub 2021 Jun 2.
Familial exudative vitreoretinopathy (FEVR), a group of rare inherited retinal vascular disorders, is the major cause of vision loss in juveniles. At present, the diagnosis of FEVR remains difficult due to its clinical and genetic heterogeneities. To identify the causative genetic variants in two unrelated FEVR-affected families: one Indian family and one Chinese Han family. Five affected patients from two families were recruited for this study. Whole-exome sequencing was applied to the probands, and Sanger sequencing was performed for validation. Stringent whole-exome sequence data analyses were performed to evaluate all of the identified pathogenic variants. Two novel variants in the gene, were identified: a missense variant c.437 T > G (p.Leu146Arg); and a nonsense variant c.477 C > A (p.Cys159*). Both variants cosegregated with the disease in the investigated FEVR-affected families. Additionally, both variants inactivated the ability of TSPAN12 protein to enhance Norrin/β-catenin signaling. This study expands the mutational spectrum of for FEVR.
家族渗出性玻璃体视网膜病变（FEVR），一组罕见的遗传性视网膜血管疾病，是青少年视力丧失的主要原因。目前，由于其临床和遗传异质性，FEVR 的诊断仍然具有挑战性。
为了鉴定两个无关的 FEVR 受累家庭的致病遗传变异：一个印度家庭和一个中国汉族家庭。本研究招募了来自两个家庭的五名受影响的患者。对先证者进行全外显子组测序，并进行 Sanger 测序验证。对所有鉴定的致病性变异进行严格的全外显子组序列数据分析。
在 基因中发现了两个新的变异：错义变异 c.437 T > G (p.Leu146Arg)；和无义变异 c.477 C > A (p.Cys159*)。这两个变异在受调查的 FEVR 受累家庭中与疾病共分离。此外，这两个变异都使 TSPAN12 蛋白增强 Norrin/β-连环蛋白信号的能力失活。
本研究扩展了 FEVR 的 基因突变谱。
