A Homozygote Mutation in S-Antigen Visual Arrestin SAG Gene in an Iranian Patient with Oguchi Type One: A Case Report

Abstract

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness (CSNB) characterized by specific features such as golden-brown discoloration of the fundus called Mizuo-Nakamura phenomenon which is distinguishable by fundoscopy, and retinography. Clinical diagnosis is confirmed through genetic test. Two known genes in pathogenesis of Oguchi disease are SAG and GRK1. A 35-year-old Iranian male exhibiting the clinical features of congenital stationary night blindness, was referred to the genetic clinic of Dr. Farhud, Tehran, Iran in 2012 and examined. Ophthalmic examination including slit-lamp biomicroscopy, perimetry and funduscopy was performed. Additionally, the full-field electroretinography and molecular testing for congenital stationary night blindness were performed. Molecular genetic tests, including the analysis of GSK1 and SAG genes exon-intron boundaries were performed for this patient and his family. According to the sequencing results, we did not find any mutation in GSK1 gene. However, a new homozygote mutation at location chr2:233320735, c.517delC, p.P96LfsX28 was identified in exon four of SAG gene. This deletion causes a frame shift mutation, and premature stop codon that results in deletion of about 281 amino acid residues of S-antigen visual arrestin protein (from entire C-terminal). This mutation was also found in patient's parents and one of his sister as heterozygote form. This is the first molecular evidence for SAG gene mutation in an Iranian family affected with Oguchi disease type 1. The identification of the new c.517delC, p.P96LfsX28 mutation in this family with Oguchi disease can confirm the pathogenicity of this variant.

Keywords: Congenital night blindness; GRK1 protein; Oguchi disease; SAG protein.

Fig. 1:

A) A part of exon four sequence of SAG gene, without C nucleotide deletion (location chr2:233320735, c.517delC, p.P96LfsX28) B) The same part of exon four of SAG gene, with C nucleotide deletion which is resulted in a frame shift mutation and premature stop codon in this gene

Fig. 2:

The normal sequencing result of SAG gene exon four in a completely healthy sister, without a heterozygote C nucleotide deletion (location chr2:233320735, c.517, p.P96LfsX28). The C nucleotide showed by arrow in this figure, was deleted in patient and parents

Fig. 3:

The sequencing result of SAG gene exon four in affected patient, with a homozygote C nucleotide deletion (location chr2:233320735, c.517delC, p.P96LfsX28)

Fig. 4:

The sequencing result of SAG gene exon four in parents and one of patient’s sister, with a heterozygote C nucleotide deletion (location chr2:233320735, c.517delC, p.P96LfsX28)