Mizuo-Nakamura Phenomenon Research Articles

Shine Amidst Darkness—A Case of Oguchi Disease

Abstract An 11-year-old boy presented with complaints of defective night vision. Visual acuity was 6/6 in both eyes. The fundus showed a golden-to-grey discoloration in light and on dark adaptation, the fundus reverted to its normal appearance demonstrating the classical Mizuo-Nakamura phenomenon. The electroretinogram showed abnormal rod responses and normal photopic responses. An electroretinogram done after overnight dark adaptation showed partial recovery with subsequent attenuation. Screening of family members showed abnormal electroretinogram findings in his father and brother. This case is portrayed on account of its rarity.

Mizuo–Nakamura phenomenon in a 10-year-old boy with Oguchi disease

Mizuo–Nakamura phenomenon in a 10-year-old boy with Oguchi disease

Genetic analysis and clinical features of three Chinese patients with Oguchi disease.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness caused by disease-causing variants in the rhodopsin kinase gene (GRK1) or the arrestin gene (SAG). Our study aims to describe the clinical features and identify the genetic defects for three Chinese patients with Oguchi disease. We conducted detailed ophthalmologic examinations for three patients from three unrelated non-consanguineous Chinese families. Targeted next-generation sequencing (targeted NGS) and copy number variations (CNVs) analysis were applied to screen pathogenic variants. Sanger sequencing validation, quantitative real-time PCR (qPCR), and segregation analysis were further performed for confirmation. Subsequently, a combined genetic and structural biology approach was used to infer the likely functional consequences of novel variants. All three patients presented with typical clinical features of Oguchi disease, including night blindness, characteristic fundus appearance (Mizuo-Nakamura phenomenon), attenuated rod responses, and negative ERG waveforms. Their visual acuity and visual field were normal. Genetic analysis revealed two pathogenic variants in SAG and four pathogenic variants in GRK1. Patient 1 was identified to harbor compound heterozygous SAG variants c.874C > T (p.R292*) and exon2 deletion. Compound heterozygous GRK1 variants c.55C > T (p.R19*) and c.1412delC (p.P471Lfs*52) were found in patient 2. In patient 3, compound heterozygous GRK1 variants c.946C > A (p.R316S) and c.1388T > C (p. L463P) were detected. We reported the first two Chinese Oguchi patients with novel GRK1 pathogenic variants (P471Lfs*52, R316S, L463P) and one Oguchi case with SAG, indicating both GRK1 and SAG are important causative genes in Chinese Oguchi patients.

Mizuo–Nakamura phenomenon in X-linked retinoschisis

PurposeTo determine whether the Mizuo–Nakamura phenomenon, which is an important diagnostic sign of Oguchi's disease, also occurs in patients with genetically proven X-linked retinoschisis (XLRS). MethodsWe examined three patients with a clinical and genetic diagnosis of XLRS and one patient who was clinically diagnosed with Oguchi's disease, with an emphasis on the Mizuo–Nakamura phenomenon. We obtained color fundus photographs, especially in the fully dark-adapted state, using the non-mydriatic mode on a digital retinal camera and infrared observation monitor to avoid the bleaching effects caused by the viewing light, which alters the fundus color in a short time. ResultsThe Mizuo–Nakamura phenomenon was observed in all patients with molecularly proven XLRS, similar to that in the patient with Oguchi's disease. The sets of photographs were obtained in the light- and dark-adapted states using our newly devised techniques needed to witness the Mizuo-Nakamura phenomenon. Conclusions and ImportanceThe Mizuo–Nakamura phenomenon was identified in three patients with genetically proven XLRS. To the best of our knowledge, this study provided the first genetic evidence of the Mizuo–Nakamura phenomenon in a patient with molecularly proven XLRS without the causative genetic abnormalities for Oguchi's disease. Our findings suggest that XLRS is responsible for the Mizuo–Nakamura phenomenon and its presence in XLRS is not a rare exception but may be a consistent manifestation of XLRS.

Oguchi's disease: two cases and literature review.

Oguchi's disease is a rare form of congenital stationary night blindness, associated with light-dependent golden fundus discoloration. In this report, we describe two cases of Oguchi's disease, both of which had two characteristic features: congenital stationary night blindness and fundoscopic manifestation of the Mizuo–Nakamura phenomenon. In both patients, fundus examination revealed a metallic sheen throughout the retina, which disappeared after 2.5 hours of dark adaptation, suggestive of the Mizuo–Nakamura phenomenon. The characteristic electroretinogram (ERG) changes (i.e., un-recordable rod response and reductions of maximal response, oscillatory potentials, and flicker response) in these patients confirmed the clinical diagnosis of Oguchi's disease. Furthermore, we discuss the results of our literature search for evidence concerning the diagnosis and pathogenesis of this rare disease. Further studies regarding the genes involved in phototransduction and light adaptation are needed to determine the pathogenesis of this rare disease.

A rare case of oguchi disease exhibiting the classic Mizuo-Nakamura phenomenon

Oguchi disease also called congenital stationary night blindness is an autosomal recessive genetic condition first identified in Japan with a few cases reported in other countries like Europe, America, India and Pakistan. We report one such case exhibiting the Mizuo-Nakamura phenomenon with a reduced amplitude on the b-wave of the rod electroretinogram advocating this diagnosis. A 40-year-old man presented with complaints of non-progressive decrease in vision as the day progressed for 6 months with normal vision during the day in both eyes. There was no history of trauma or any other ocular or systemic disease. His parents had a second-degree consanguineous marriage and his father experienced similar symptoms. Visual acuity for distance was 6/6 and N6 for near in both eyes. His anterior segment and posterior segments were normal. When the patient was put to dark adaptation for 3 hours, there was a change in his fundus background colour from grey to red (Mizuo-Nakamura phenomenon). The b-wave amplitude was decreased on the rod electroretinogram. The cone electroretinogram on the other hand was normal. All this was confirmed by his genetic study which favoured this diagnosis.This disease presents with features similar to retinitis pigmentosa in terms of mutations in the SAG gene This highlights the importance of the Mizou-Nakamura phenomenon in formulating a confirmatory diagnosis and treatment protocol.

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.

Progression from Classical Oguchi Disease to Retinitis Pigmentosa after 50 Years

Fundus photograph of a 77-year-old Japanese man with retinitis pigmentosa (RP) and homozygous c.636delT in S-antigen (SAG) (Fig A). The patient’s condition had been reported as Oguchi disease (Fig B) with Mizuo-Nakamura phenomenon at the 20th International Congress of Ophthalmology held at Munich in 1966. Fundus photograph of the same patient taken around that time (age ∼23) showed metallic sheen covering the posterior pole with no sign of retinal degeneration. These photographs mark the first example of progression of classical juvenile Oguchi disease to RP.

Mizuo-Nakamura phenomenon in an Indian male.

Key Clinical Message The authors present a 20‐year‐old myopic male who showed golden color of fundus (Mizuo‐Nakamura phenomenon) in light and normal color after long dark adaptation. This phenomenon is associated with an abnormally slow dark adaptation and is typically noted in Oguchi disease, a variant of congenital stationary night blindness.

Oguchi type I caused by a homozygous missense variation in the SAG gene

Oguchi disease, is a very rare form of night blindness caused by biallelic variations in the SAG or GRK1 genes, both involved in rod restoration after light stimuli. Here we report the clinical and genetic findings of an 8-year old boy with a history of reduced visual acuity, nyctalpia and hemeralopia. Clinical findings, in particular the Mizuo-Nakamura phenomenon, were compatible with a diagnosis of Oguchi disease. Genetic testing revealed a novel missense homozygous variation in the SAG gene. This is the first evidence that the disease can be caused by missense variations in this gene.

Oguchi disease masked by retinitis pigmentosa

The purpose of this study was to report a patient with Oguchi disease whose ophthalmological characteristics were masked by retinitis pigmentosa (RP). The method used in this study was case report. A 53-year-old man had a progressive decrease in his visual acuity and was diagnosed with RP because of night blindness, fundoscopic findings, ring scotoma, and extinguished single-flash electroretinograms (ERGs). However, a faint golden-yellowish reflex of the retina prompted us to make a more detailed examination of the fundus after a long period of dark adaptation, ERGs, and genetic analysis. Examinations showed the Mizuo-Nakamura phenomenon, relative intact photopic ERGs, and a SAG mutation, and the patient was diagnosed with RP associated with Oguchi disease. When RP accompanies Oguchi disease, the clinical characteristics of Oguchi disease might be masked. In such a situation, the correct diagnosis is difficult. However, careful analysis of clinical findings will suggest Oguchi disease, which can be confirmed by molecular genetics.

Mizuo-Nakamura phenomenon in Oguchi disease due to a homozygous nonsense mutation in the SAG gene

Mizuo-Nakamura phenomenon in Oguchi disease due to a homozygous nonsense mutation in the SAG gene

Spectral-Domain Optical Coherence Tomography Findings in the Mizuo–Nakamura Phenomenon of Oguchi Disease

Spectral-Domain Optical Coherence Tomography Findings in the Mizuo–Nakamura Phenomenon of Oguchi Disease

Syndrome d’Oguchi ou cécité nocturne congénitale stationnaire : à propos d’un cas

Oguchi disease, originally described in Japanese people, is a rare form of stationary night blindness in patients with normal acuity. We report the case of an 8-year-old girl who presented with an abnormal terrified behavior in the dark. Thorough questioning revealed hemeralopia. Her clinical examination (visual acuity, Goldmann visual field, and color vision) were normal. The fundus examination showed golden-brown color, grayish, almost greenish yellow discoloration in the peripheral area with no osteoclast. This abnormality disappeared after prolonged dark adaptation. The electroretinogram showed a reduced b wave amplitude under scotopic conditions. Her parents were cousins. This diagnosis should be suggested when hemeralopia is associated with typical fundus aspect resolving after dark adaptation (so called Mizuo-Nakamura phenomenon). The long-term prognosis in these patients is good in the absence of clinical progression. This is a genetic autosomal recessive disease caused by mutations in the gene coding for arrestin located in 2q37.1.

Doença de Oguchi: relato de caso e revisão bibliográfica

Relatamos o caso de uma paciente com sintomas de cegueira noturna congenita estacionaria (CNCE) no qual constatamos alteracoes oftalmoscopicas peculiares da doenca de Oguchi, inedita, nos limites de nosso conhecimento, a consideracao da literatura medica brasileira publicada. Observamos e documentamos as alteracoes classicas desta doenca e do seu importante comemorativo, o tambem infrequente, fenomeno de Mizuo-Nakamura. O exame eletrorretinografico (ERG) tambem mostrou sinais tipicos. Acrescentamos, brevemente, revisao bibliografica da doenca.

Oguchi disease with sectoral retinitis pigmentosa harboring adenine deletion at position 1147 in the arrestin gene

To report a Japanese patient with Oguchi disease and sectoral retinitis pigmentosa harboring a homozygous adenine deletion at position 1147 (1147delA) in the arrestin gene. Case report. In both eyes, golden discoloration with Mizuo-Nakamura phenomenon and tapetoretinal degeneration of the fundus were exhibited. Electroretinography showed abnormal a-wave and absent b-wave. The presence of 1147delA in the arrestin gene was demonstrated. Our case provides further evidence of the close association of 1147delA in the arrestin gene in Japanese patients with Oguchi disease. Coexpression of both phenotypes of Oguchi disease and retinitis pigmentosa may suggest the possible involvement of additional defects of genes encoding the phototransduction proteins.

Oguchi disease: phenotypic characteristics of patients with the frequent 1147delA mutation in the arrestin gene.

To characterize clinical features of patients with Oguchi disease associated with a homozygous deletion of adenine at nucleotide 1147 (1147delA) in codon 309 in the arrestin gene. Mutation screening by single-strand conformation polymorphism analysis was done, followed by sequencing. Ophthalmologic testing included evaluation of visual acuity and color vision, fundus examination, electroretinography, fluorescein angiography, evaluation of kinetic visual field, and dark adaptometry. Nine patients with Oguchi disease from seven unrelated families and family members who were unaffected by the disease were examined. A homozygous 1147delA mutation in the arrestin gene was identified in eight patients from six families with Oguchi disease. All patients who were examined exhibited a golden-yellow retinal reflex associated with Mizuo-Nakamura phenomenon and impairment of rod function in dark adaptation tests, although fundus examination showed slight variation in these findings. Four patients with the mutation had slightly reduced visual acuity, and the electroretinograms of three patients showed slightly reduced amplitudes during 30-Hz flicker electroretinography. Patients with Oguchi disease associated with the arrestin 1147delA mutation typically demonstrate retarded rod adaptation, whereas some patients have slightly impaired cone function.

Mizuo Phenomenon in X-linked Retinoschisis

Four unrelated males with X-linked retinoschisis and a golden fundus reflex had Mizuo-Nakamura phenomenon, which, to our knowledge, has been described only in Oguchi's disease and X-linked cone dystrophy. These findings, together with experimental observations and data from the literature, led us to hypothesize that the Mizuo-Nakamura phenomenon is caused by an excess of extracellular potassium in the retina as a result of a decreased potassium scavenging capacity of retinal Müller cells.

X-linked Recessive Cone Dystrophy With Tapetal-like Sheen

We encountered a new X-linked recessive cone dystrophy in which patients have a greenish-golden tapetal-like sheen of the retina; while the retinal sheen and electroretinographic abnormalities are present from childhood, patients are not symptomatic until adult years. All of the male patients tested showed evidence of cone dysfunction on color vision testing, dark adaptometry, and electroretinography. After three hours of dark adaptation, the tapetal-like sheen disappeared, with most areas changing from greenish-golden shades to orange-red hues (Mizuo-Nakamura phenomenon). One male patient had a retinal detachment from atrophic round holes in the equatorial retina.