Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy

Li-Yun Jia,Kai Ma

doi:10.1186/s12886-021-01852-3

Abstract

PurposeThis study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features.MethodsThirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments.ResultsFour novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5’UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100).ConclusionsOur results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

Highlights

Familial exudative vitreoretinopathy (FEVR) is an inherited vitreous retinal disease characterized by incomplete vascularization of the peripheral retina with secondary complications including dragged retina, exudation, vitreous hemorrhage, and retinal detachment [1, 2]
Genes involved in the pathogenesis of FEVR include FZD4, NDP, lipoprotein receptorrelated protein-5 (LRP5), TSPAN12, ZNF408, KIF11, and CTNNB1 [4,5,6,7,8,9]
The DNAs from the 33 FEVR patients were analyzed for mutations in the three exons and flanking exon-intron boundaries of NDP gene

Summary

Introduction

Familial exudative vitreoretinopathy (FEVR) is an inherited vitreous retinal disease characterized by incomplete vascularization of the peripheral retina with secondary complications including dragged retina, exudation, vitreous hemorrhage, and retinal detachment [1, 2]. Genes involved in the pathogenesis of FEVR include FZD4, NDP, LRP5, TSPAN12, ZNF408, KIF11, and CTNNB1 [4,5,6,7,8,9]. The Norrie disease gene (NDP) is located on chromosome Xp11.2–11.3 and encodes for the 133-amino-acid. Over 160 mutations of the NDP gene have been reported so far, most of which are missense mutations. Some nonsense, splicing site, insertion, deletioninsertion, and regulatory region mutations are reported in the NDP gene. Most patients with NDP gene mutations show the Norrie disease phenotype; only 5% of patients show FEVR. Mutation screening of the NDP gene in our Chinese patients with FEVR could, determine further enrich the spectrum and frequency of mutations in NDP-causing FEVR

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