The characteristics of digenic familial exudative vitreoretinopathy

  • Yian LiEmail author
  • Jie Peng
  • Jiakai Li
  • Qi Zhang
  • Jing Li
  • Xiang Zhang
  • Ping Fei
  • Kaiqin She
  • Peiquan Zhao



To describe and analyse the clinical and genetic characteristics of digenic familial exudative vitreoretinopathy (FEVR).


The study cohort consisted of patients with FEVR (n = 13) to identify patients with two mutations in two different genes. A genetic analysis of the LRP5, FZD4, TSPAN12, and ZNF408 genes was performed with next-generation sequencing (NGS). The genotype data obtained from the patients with FEVR were analysed and correlated with their clinical manifestations. They were then further evaluated in conjunction with other data that were available for these genes. The probands and parents/relatives underwent comprehensive age-appropriate ophthalmic examinations.


The medical history and genetic reports of 487 patients with FEVR were reviewed. In all, we identified 13 probands (2.67%, 13/487) with simultaneous mutations in two disease-causing genes. A total of 25 of mutations were found, including10 in FZD4, 8 in LRP5, 3 in ZNF408, 2 in NDP, and 2 in TSPAN12. The most frequent mutations were those in FZD4 and LRP5. We identified 8 mutations that had previously been identified and 17 novel variants. Among 26 eyes, 65.38% exhibited a phenotype, and 10 (38.46%) were stage 4, while 7 (26.92%) were stage 5.


This is the first study to report a group of patients with digenic FEVR. In most affected eyes, the stage was more severe than stage 3. We speculate that the phenotype of FEVR is more severe in patients with digenic rather than monogenic variants of FEVR-related genes.


FEVR Gene Digenic FEVR Phenotype 



This research was supported by the National Natural Science Foundation Project of China (81770964, 15XD1502800).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Informed consent

Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yian Li
    • 1
    Email author
  • Jie Peng
    • 1
  • Jiakai Li
    • 1
  • Qi Zhang
    • 1
  • Jing Li
    • 1
  • Xiang Zhang
    • 1
  • Ping Fei
    • 1
  • Kaiqin She
    • 1
  • Peiquan Zhao
    • 1
  1. 1.Department of OphthalmologyXinhua Hospital affiliated to Shanghai Jiaotong University School of MedicineShanghaiChina

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