A Homozygote Mutation in S-Antigen Visual Arrestin SAG Gene in an Iranian Patient with Oguchi Type One: A Case Report
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.
2. Yamamoto S SK, Berson EL, Dryja TP (1997). Defects in the rhodopsin kinase gene in the Oguchi form of stationary night blindness. Nat Genet, 15:175-8.
3. Yamamoto H SA, Eriksson U, Harris E, Berson EL, Dryja TP (1999). Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat Genet, 22:188-91.
4. Fuchs S NM, Maw M, Tamai M, Oguchi Y, Gal A (1995). A homozygous 1–base pair deletion in the arrestin gene is a frequent cause of Oguchi disease in Japanese. Nat Genet, 10:360-2.
5. Sergouniotis P DA, Sehmi K, Webster A, Robson A, Moore A (2011). Mizuo-Nakamura phenomenon in Oguchi disease due to a homozygous nonsense mutation in the SAG gene. Eye (Lond), 25:1098-1101.
6. Nakamura M YS, Okada M, Ito S, Tano Y, Miyake Y (2004). Novel mutations in the arrestin gene and associated clinical features in Japanese patients with Oguchi's disease. Ophthalmology, 111:1410-4.
7. Nakazawa M WY, Tamai M (1998). Arrestin gene mutations in autosomal recessive retinitis pigmentosa. Arch Ophthalmo, 116:498-501.
8. Waheed NK QA, Malik SN, Maria M al (2012). A nonsense mutation in S-antigen (p. Glu306*) causes Oguchi disease. Mol Vis, 18:1253-1259.
9. Hayashi T GT, Takeuchi T, Goto-Omoto S, Kitahara K (2007). A novel homozygous GRK1 mutation (P391H) in 2 siblings with Oguchi disease with markedly reduced cone responses. Ophthalmology, 114:134-41.
10. Zhang Q ZF, Riazuddin SA, Xiao X et al (2005). A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene. Mol Vis, 11:977-85.
11. Maw MA JS, Jablonka S, Müller B et al (1995). Oguchi disease: suggestion of linkage to markers on chromosome 2q. J Med Genet, 32:396-398.
12. K (1977). Congenital color vision defects. Krill’s Hereditary Retinal and Choroidal Diseases. , 2:355-90.
13. Singh JR (1990). Genetic heterogeneity of Oguchi's disease. Indian J Ophthalmol, 38(4):193-4.
14. TP. D (2000). Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture. Am J Ophthalmol, 130:547-63.
15. Mendonça RHFd AS, Plateroti R, Plateroti P, Ferreira EL (2013). Electrophysiological findings in Oguchi disease. Klin Monbl Augenheilkd, 72:188-90.
16. Miyake Y YK, Horiguchi M, Kawase Y, Kanda T (1986). Congenital stationary night blindness with negative electroretinogram. Arch Ophthalmol, 104:1013-20.
17. SNYDER C (1963). Jean Nougaret, the butcher from Provence, and his family. Archives of Ophthalmology, 69:676-8.
18. Teke MY, Kabacam S, Demircan S, Alikasifoglu M (2016). A novel missense mutation of the GRK1 gene in Oguchi disease. Mol Med Rep, 14:3129-33.
19. Maw M KG, Kar B, John S, Bridges R, Denton M (1998). Two Indian siblings with Oguchi disease are homozygous for an arrestin mutation encoding premature termination. Hum Mutat, Suppl 1:S317-9.
20. Waheed NK QA, Malik SN, Maria M et al (2012). A nonsense mutation in S-antigen (p.Glu306*) causes Oguchi disease. Mol Vis, 18:1253-1259.
|Issue||Vol 49 No 5 (2020)|
|Congenital night blindness; Oguchi disease; GRK1 protein; SAG protein|
|Rights and permissions|
|This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.|