Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, Henan Key Laboratory of Ophthalmology and Visual Science, People's Hospital of Zhengzhou University, People's Hospital of Henan University, No. 7 Weiwu Road, Zhengzhou, 450000, Henan, China.
BMC Med Genomics. 2022 Mar 11;15(1):54. doi: 10.1186/s12920-022-01204-0.
Familial exudative vitreoretinopathy (FEVR) is a complex form of blindness-causing retinal degeneration. This study investigated the potential disease-causing variants in 20 Chinese families with FEVR.
All available family members underwent detailed ophthalmological examinations, including best-corrected visual acuity and fundus examination. All probands and most family members underwent fluorescein fundus angiography. Twenty probands underwent whole exome sequencing; 16 of them also underwent copy number variant and mitochondrial genome analysis. Bioinformatics analysis and Sanger sequencing of available family members were used to confirm the disease-causing gene variant.
Twenty families were diagnosed with FEVR based on clinical symptoms, fundus manifestations, and fundus fluorescein angiography. Whole exome sequencing revealed 14 variants in NDP, FZD4, LRP5, and TSPAN12 genes among the 13 families. These variants were predicted to be damaging or deleterious according to multiple lines of prediction algorithms; they were not frequently found in multiple population databases. Seven variants had not previously been reported to cause FEVR: c.1039T>G p.(Phe347Val) in the FZD4 gene; c.1612C>T p.(Arg538Trp) and c.3237-2A>C in the LRP5 gene; and c.77T>A p.(Ile26Asn), c.170dupT p.(Leu57Phe fsTer60), c.236T>G p.(Met79Arg) and c.550dupA p.(Arg184Lys fsTer16) in the TSPAN12 gene. We did not detect any variants in the remaining seven families.
These results expand the spectrum of variants in the NDP, FZD4, LRP5, and TSPAN12 genes and provide insights regarding accurate diagnosis, family genetic counseling, and future gene therapy for FEVR.
家族性渗出性玻璃体视网膜病变（FEVR）是一种致盲性视网膜变性的复杂形式。本研究调查了 20 个中国 FEVR 家系中潜在的致病变异。
所有可利用的家族成员均接受详细的眼科检查，包括最佳矫正视力和眼底检查。所有先证者和大多数家族成员均接受荧光素眼底血管造影。20 个先证者接受全外显子组测序；其中 16 个还接受了拷贝数变异和线粒体基因组分析。利用生物信息学分析和可利用家族成员的 Sanger 测序来确认致病基因突变。
根据临床症状、眼底表现和眼底荧光素血管造影，20 个家系被诊断为 FEVR。全外显子组测序在 13 个家系中发现 NDP、FZD4、LRP5 和 TSPAN12 基因中的 14 个变异。根据多种预测算法，这些变异被预测为有害或致病变异；它们在多个人群数据库中并不常见。有 7 个变异以前没有报道过导致 FEVR：FZD4 基因中的 c.1039T>G p.(Phe347Val)；LRP5 基因中的 c.1612C>T p.(Arg538Trp)和 c.3237-2A>C；以及 TSPAN12 基因中的 c.77T>A p.(Ile26Asn)、c.170dupT p.(Leu57Phe fsTer60)、c.236T>G p.(Met79Arg)和 c.550dupA p.(Arg184Lys fsTer16)。我们在其余的 7 个家系中没有检测到任何变异。
这些结果扩展了 NDP、FZD4、LRP5 和 TSPAN12 基因中的变异谱，为 FEVR 的准确诊断、家族遗传咨询和未来的基因治疗提供了线索。
