Targeted Resequencing Identifies Pathogenic Variants in Previously Unresolved Familial Exudative Vitreoretinopathy Cases

Authors

• Marcus Yaldo, Oakland University William Beaumont School of Medicine Medical Student
• Savyo Krikor
• Wendy A. Dailey
• Cecille Pinnock
• Victoria Jobczyk
• Kimberly A. Drenser, Corewell Health East
• Kenneth P. Mitton

Document Type

Conference Proceeding

Publication Date

6-2026

Publication Title

Investigative Ophthalmology and Visual Science

Abstract

Purpose :
Resequencing with an expanded 30-gene panel to identify pathogenic variants in 12 subjects with Familial Exudative Vitreoretinopathy (FEVR) who were previously sequenced with an 8-gene Ampliseq panel.

Methods :
Subjects (12) with clinical or suspected Familial Exudative Vitreoretinopathy (FEVR) who previously underwent 8-gene panel sequencing without a definitive molecular discovery were re-sequenced using a custom 30-gene targeted panel (total targeted region 234,614 bp across 817 regions). Genes included twenty FEVR-linked genes implicated in retinal vascular development. Genomic DNA was quantified using Qubit fluorometry and prepared with a custom Celemics Enzymatic DNA Prep Kit. Library concentration and fragment size were assessed using Agilent TapeStation analysis. Sequencing was performed on an Illumina iSeq100 using paired-end reads. Variant call files were analyzed using Ensembl GRCh37 for transcript-based consequences, population allele frequencies were obtained from gnomAD, and clinical significance was derived from ClinVar.

Results :
Expanded resequencing identified pathogenic and likely pathogenic variants not detected by prior 8-gene sequencing. Pathogenic variants detected in the cohort included a splice donor variant in LRP5 (c.4488+2T>G), a stop-gain variant in CTNNB1 (p.Gln623Ter), a stop-gain variant in KCNJ13 (p.Trp53Ter), and a splice donor variant in VCAN. Additional patients carried pathogenic or likely pathogenic LRP5 missense variants such as Thr852Met and Thr271Met. Several notable variants of uncertain significance were detected in FEVR related genes, including ZNF408 p.Ser225Phe, CAPN5, CTNND1, DLG1, and a FZD4 missense variant (p.Gly161Arg). Many patients exhibited combinations of variants across multiple canonical and candidate FEVR associated genes.

Conclusions :
Expanded 30-gene panel sequencing identified pathogenic and clinically relevant variants in patients with Familial Exudative Vitreoretinopathy who previously lacked identifiable pathogenic findings, supporting its utility as a complementary approach to improve molecular diagnostic yield.

Volume

67

Issue

7

First Page

5306

Comments

Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting, May 3-7, 2026, Denver, CO

Last Page

5306

Recommended Citation

Yaldo M, Krikor S, Dailey WA, Pinnock C, Jobczyk V, Drenser KA, et al. Targeted resequencing identifies pathogenic variants in previously unresolved familial exudative vitreoretinopathy cases. Invest Ophthalmol Vis Sci. 2026 Jun;67(7):5306.