Mutation Analysis of FZD4, NDP, and LRP5 in Familial Exudative Vitreoretinopathy Patients

Abstract

Purpose: : Familial exudative vitreoretinopathy: FEVR, MIM133780 is an inherited retinal disorder characterized by abnormal peripheral vascurization. FEVR was first described by Criswick and Schepens (1969). Mutations in FZD4, NDP, and LRP5 are responsible for this disorder. The purpose of this study was to screen these three genes in Japanese FEVR patients for genetic diagnosis.

Methods: : Genomic DNA was extracted from leukocytes of peripheral blood of 7 patients in 5 families and 100 unaffected subjects according to standard procedures, with informed consent. We amplified the cording region of FZD4, NDP, and LRP5 genes from genomic DNAs of the patients using a PCR method, and the dye terminator method was used for sequencing.

Results: : H69Y, P104T, and G530E mutations of FZD4 were observed in one of each family, but there were no patients in NDP or LRP5 mutation. The P104T of FZD4 was a conserved amino acid mutation. This mutation was not observed in 100 subjects in the control group and appeared to be a novel mutation associated with FEVR. The G530E mutation of FZD4 was observed in affected and unaffected family member.

Conclusions: : Mutation analysis of FZD4, NDP, and LRP5 for the diagnosis of familial exudative vitreoretinopathy is thought to be useful, but FZD4 G530E and no mutation cases suggest that other genes for FEVR to be identified remain.

Keywords: genetics • gene screening • retina