Oguchi Disease 1

A number sign (#) is used with this entry because of evidence that Oguchi disease-1 (CSNBO1) is caused by homozygous or compound heterozygous mutation in the arrestin gene (SAG; 181031) on chromosome 2q37.

Description

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness in which all other visual functions, including visual acuity, visual field, and color vision, are usually normal. A typical feature of the disease is a golden or gray-white discoloration of the fundus that disappears in the dark-adapted state and reappears shortly after the onset of light (Mizuo phenomenon, or Mizuo-Nakamura phenomenon). The course of dark adaptation of rod photoreceptors is extremely retarded, whereas that of cones appears to proceed normally (summary by Fuchs et al., 1995).

Genetic Heterogeneity of Oguchi Disease

Oguchi disease-2 (CSNBO2) is caused by mutation in the rhodopsin kinase gene (GRK1; 180381) on chromosome 13q34.

Clinical Features

Oguchi disease is characterized by congenital static night blindness and diffuse yellow or gray coloration of the fundus. After 2 or 3 hours in total darkness, the normal color of the fundus returns (Oguchi, 1907; Mizuo, 1913; Carr and Ripps, 1967).

Maw et al. (1998) reported 2 Indian brothers with night blindness from an early age. The 28-year-old brother demonstrated the distinctive Mizuo-Nakamura phenomenon (light-dependent golden fundus discoloration) and normal photopic and 30-Hz flicker electroretinogram (ERG) responses; under scotopic conditions, a white flash elicited a negative wave, whereas the response to a blue flash was extinguished. The 18-year-old brother had similar findings in his right eye, whereas in his left eye visual acuity was markedly decreased, both scotopic and photopic ERGs were extinguished, and fundus examination showed macular degeneration, mottled retinal pigment epithelium in the posterior pole and midperiphery, vitreous floaters, pale disc, and sheathed, attenuated vessels.

Nakamura et al. (2004) studied 2 unrelated Japanese men, aged 23 and 30 years, who both had night blindness from childhood and also exhibited the Mizuo-Nakamura phenomenon, with golden-yellow discoloration throughout the posterior pole out to the equatorial region. Full-field ERGs elicited by Ganzfeld stimuli after 30 minutes of dark adaptation were nonrecordable in both patients, whereas photopic ERG responses and amplitudes of the 30-Hz flicker ERG were within normal limits. The bright-flash mixed rod-cone ERGs demonstrated a 'negative' configuration with reduced a-wave amplitudes and nearly absent b-wave. Oscillatory potentials were present in both patients.

Mapping

Maw et al. (1995) considered the gene encoding S antigen (SAG; 181031), also known as arrestin, to be a plausible candidate gene for Oguchi disease because the gene appeared to be involved in the recovery phase of light transduction (Palczewski et al., 1989; Palczewski et al., 1992). The SAG gene had previously been mapped to 2q37.1. Maw et al. (1995) found linkage of Oguchi disease to markers that mapped to distal 2q in an inbred Indian kindred. The segregation data suggested that 3 affected sisters were homozygous by descent for a region between D2S172 and D2S345. An intragenic SAG polymorphism was homozygous in all affected persons and a recombination event suggested that SAG maps proximal to D2S345. Collectively, the findings supported the suggestion that a defect in S antigen is responsible for Oguchi disease.

Molecular Genetics

Fuchs et al. (1995) identified a homozygous 1-bp deletion in the SAG gene (1147delA; 181031.0001) in 5 of 6 unrelated Japanese patients with Oguchi disease.

Nakazawa et al. (1998) reported 2 sibs with the SAG 1147delA mutation: one had Oguchi disease and the other had retinitis pigmentosa (RP47; 613758).

In an Indian family in which 2 brothers had Oguchi disease, Maw et al. (1998) performed SSCP screening of the arrestin gene, which revealed a bandshift in exon 8 that was homozygous in the 2 patients, heterozygous in the unaffected parents and an unaffected sister, and absent in 80 Indian controls. Sequencing identified a nonsense mutation (R193X; 181031.0002) that segregated with disease in the family. Noting that some Oguchi patients with congenital night blindness subsequently undergo progressive pigmentary retinal degeneration, as seen in the 18-year-old brother, Maw et al. (1998) suggested that similar molecular pathologic events might be responsible for pigment formation in both Oguchi disease and some cases of retinitis pigmentosa.

In 2 unrelated Japanese men with Oguchi disease, Nakamura et al. (2004) identified compound heterozygosity and homozygosity, respectively, for mutations in the SAG gene (258100.0001, 258100.0003 and 258100.0004). The authors noted that all of the known arrestin gene mutations associated with Oguchi disease were nonsense mutations or frameshift mutations with premature terminations that are likely null alleles, suggesting that only critical mutations cause the disorder.

In a 15-year-old Pakistani girl with typical Oguchi disease, Waheed et al. (2012) identified homozygosity for a nonsense mutation (E306X; 181031.0005) in the SAG gene that was present in heterozygosity in her unaffected mother and 4 other unaffected relatives and was not found in a healthy control panel from the same population. The authors noted that the patient was also diagnosed with dural sinus thrombosis, thrombocytopenia, and systemic lupus erythematosus, which were not likely to be associated with the SAG variant. In addition, the patient, as well as 4 other family members, had hyperhomocysteinemia, which was found to segregate with the known 677C-T polymorphism in the MTHFR gene (607093.0003).