Whole-Exome Sequencing Reveals Novel NDP Variants in X-Linked Familial Exudative Vitreoretinopathy

摘要

Purpose To investigate causative variants in three Chinese families affected with familial exudative vitreoretinopathy (FEVR). Methods Three unrelated Chinese families were recruited in this study. The three probands and their family members experienced a comprehensive age-appropriate eye examination and genetic analysis. Luciferase assay was performed to evaluate impacts of variants on Norrin/beta-catenin signaling activity. Results Here we report two novel NDP variants associated with FEVR in three families, including c.17T>C (p.Leu6Pro) in family 1 and c.58G>A (p.Gly20Arg) in family 2 and 3. These two variants were co-segregated with the disease phenotypes within each family. In addition, both variants resulted in compromised Norrin/beta-catenin signaling activity. Conclusion Our study identified two FEVR-associated pathogenic variants in NDP, which expanded the variant spectrum and provided information for the genetic diagnosis of FEVR.