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. 2022 Apr 1;63(4):7.
doi: 10.1167/iovs.63.4.7.

FZD4 in a Large Chinese Population With Familial Exudative Vitreoretinopathy: Molecular Characteristics and Clinical Manifestations

Jinglin Lu  1 , Li Huang  1 , Limei Sun  1 , Songshan Li  1 , Zhaotian Zhang  1 , Zhaoxin Jiang  1 , Jiaqing Li  1 , Xiaoyan Ding  1
Affiliations

FZD4 in a Large Chinese Population With Familial Exudative Vitreoretinopathy: Molecular Characteristics and Clinical Manifestations

Jinglin Lu et al. Invest Ophthalmol Vis Sci. .

Abstract

Purpose: The purpose of this study was to establish a genotype-phenotype correlation of familial exudative vitreoretinopathy (FEVR) caused by FZD4 gene mutations.

Methods: Six hundred fifty-one probands and their family members were recruited based on a clinical diagnosis of FEVR between 2015 and 2021 at Zhongshan Ophthalmic Center. Ocular examinations were performed in all participants. Targeted gene panel sequencing and whole-exome sequencing were performed in the probands, and Sanger sequencing was used to verify the mutations and segregation analysis was performed in the family members.

Results: Fifty-one FZD4 mutations (24 novels and 27 known) were detected in 84 families. Of these 168 eyes with FEVR, the eyes at stages 1, 2, 3, 4, and 5 were 29 (17.3%), 15 (8.9%), 19 (11.3%), 55 (32.7%), and 12 (7.1%), respectively. Exact stage of 38 (22.6%) eyes could not be determined. The FEVR phenotypes were more severe in the probands than the phenotypes in the family members (P < 0.001). The families were divided into two groups, probands that inherited the variant from the mother, and probands that inherited the variant from the father. In addition, the FEVR stage differences between these two groups were different (P < 0.05). Despite the mutations being located in different domains of FZD4, no significant differences were identified among the domains in terms of FEVR staging, retinal folds, retinal detachment, temporal midperipheral vitreoretinal interface abnormality, and foveal hypoplasia.

Conclusions: The FZD4 probands had severer phenotype than the family members, and the FEVR stage difference was greater between the probands and mothers than that between the probands and fathers.

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Conflict of interest statement

Disclosure: J. Lu, None; L. Huang, None; L. Sun, None; S. Li, None; Z. Zhang, None; Z. Jiang, None; J. Li, None; X. Ding, None

Figures

Figure 1.
Figure 1.
Schematic diagram of FZD4 domains and mutations detected in this study.
Figure 2.
Figure 2.
FEVR stages of bilateral eyes. (A) FEVR stages of all the probands. (B) FEVR stages between probands and family members. OD, right eye; OS, left eye.
Figure 3.
Figure 3.
Fundus images of probands and family members. A, B, and C are from the family DX684 with the c.313A>G (p.Met105Val) variant. (A) Fundus image and fundus fluorescein angiography (FFA) of the proband DX684 indicates prominent macular dragging and ectopic macula. (B) FFA of the brother of DX684 indicates supernumerary branching. (C) FFA of the mother of DX684 indicates supernumerary branching. (D) FFA of the mother of DX684 was unremarkable. D and E are from the family DX342 with the c.1034_1054del (p.Ser345_Ala351del) variant. D FFA of the proband DX342 indicates macular dragging, ectopic macula, supernumerary branching, and coloboma of the choroid. (E) FFA of the father of DX342 indicates peripheral avascular retinal area and supernumerary branching. F and G are from the family XDW41 with the c.1000-1001insCTCA (p.Lys334Thrfs*6) variant. (F) Fundus images of the proband XDW41 indicate retinal folds in the right eye, macular dragging, and ectopic macula in the left eye. (G) FFA of the mother of XDW41 indicates supernumerary branching.
Figure 4.
Figure 4.
Representative fundus images of probands with the same variant, 1589G>A (Gly530Glu). (A) FFA of QT2446 indicates rhegmatogenous retinal detachment. (B) FFA of QT2341 indicates supernumerary branching.
See this image and copyright information in PMC

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