PDF(Pubmed)
Abstract：
To report the novel causative variants in five Chinese families with familial exudative vitreoretinopathy (FEVR).
Five unrelated Chinese families diagnosed with FEVR were enrolled in this study. Ocular examinations and genetic analysis were performed on the probands and family members. Luciferase assay was performed to evaluate the variants\' impacts on Norrin/β-catenin signaling activity.
Five novel variants, including two frameshifts, c.518delA (p.Glu173Glyfs*42) and c.719delT (p.Leu240Profs*21), two missenses, c.482G>T (p.Gly161Val) and c. 614G>C (p. Gly205Ala), and one nonsense, c.375G>A (p.Trp125*), were identified in the TSPAN12 gene in this study. All the variants were co-segregated within each family and were predicted as pathogenic in silico. The luciferase assay showed all variants lead to various degrees of compromised Norrin/β-catenin signaling activity.
Our study expanded the variant spectrum and provided information for the genetic testing of FEVR by showing five novel FEVR-associated pathogenic variants in TSPAN12.
Our study expanded the spectrum of FEVR-associated TSPAN12 variants and further supported the inclusion of TSPAN12 gene in the evaluation of cases concerning for FEVR.
Five unrelated Chinese families diagnosed with FEVR were enrolled in this study. Ocular examinations and genetic analysis were performed on the probands and family members. Luciferase assay was performed to evaluate the variants\' impacts on Norrin/β-catenin signaling activity.
Five novel variants, including two frameshifts, c.518delA (p.Glu173Glyfs*42) and c.719delT (p.Leu240Profs*21), two missenses, c.482G>T (p.Gly161Val) and c. 614G>C (p. Gly205Ala), and one nonsense, c.375G>A (p.Trp125*), were identified in the TSPAN12 gene in this study. All the variants were co-segregated within each family and were predicted as pathogenic in silico. The luciferase assay showed all variants lead to various degrees of compromised Norrin/β-catenin signaling activity.
Our study expanded the variant spectrum and provided information for the genetic testing of FEVR by showing five novel FEVR-associated pathogenic variants in TSPAN12.
Our study expanded the spectrum of FEVR-associated TSPAN12 variants and further supported the inclusion of TSPAN12 gene in the evaluation of cases concerning for FEVR.
摘要：
■报告五个家族性渗出性玻璃体视网膜病变（FEVR）中国家庭的新型致病变异。
■本研究纳入了5个诊断为FEVR的无关中国家庭。对先证者和家庭成员进行了眼部检查和遗传分析。进行荧光素酶测定以评估变体对Norrin/β-catenin信号活性的影响。
■五个新颖的变体，包括两个移相者，c.518delA（p。Glu173Glyfs*42）和c.719delT（p。Leu240Profs*21），两个错觉，c.482G>T（p。Gly161Val）和c。614G>C（p。Gly205Ala)，还有一个废话，c.37G>A（p。Trp125*),在本研究中在TSPAN12基因中鉴定。所有变体在每个家族内共分离,并在计算机上预测为致病性的。荧光素酶测定显示所有变体导致不同程度的Norrin/β-catenin信号转导活性受损。
■我们的研究通过显示TSPAN12中五个新颖的FEVR相关致病变异，扩展了变异谱，并为FEVR的遗传测试提供了信息。
■我们的研究扩大了FEVR相关TSPAN12变异的范围，并进一步支持将TSPAN12基因纳入有关FEVR的病例评估中。
■本研究纳入了5个诊断为FEVR的无关中国家庭。对先证者和家庭成员进行了眼部检查和遗传分析。进行荧光素酶测定以评估变体对Norrin/β-catenin信号活性的影响。
■五个新颖的变体，包括两个移相者，c.518delA（p。Glu173Glyfs*42）和c.719delT（p。Leu240Profs*21），两个错觉，c.482G>T（p。Gly161Val）和c。614G>C（p。Gly205Ala)，还有一个废话，c.37G>A（p。Trp125*),在本研究中在TSPAN12基因中鉴定。所有变体在每个家族内共分离,并在计算机上预测为致病性的。荧光素酶测定显示所有变体导致不同程度的Norrin/β-catenin信号转导活性受损。
■我们的研究通过显示TSPAN12中五个新颖的FEVR相关致病变异，扩展了变异谱，并为FEVR的遗传测试提供了信息。
■我们的研究扩大了FEVR相关TSPAN12变异的范围，并进一步支持将TSPAN12基因纳入有关FEVR的病例评估中。
