A 5-year-old Syrian female was born with Oguchi disease: a rare case report.

Oguchi disease is a rare autosomal recessive disease that causes congenital stationary blindness, which is distinguished by the Mizuo-Nakamura phenomenon and caused by mutations of rhodopsin kinase gene or the arrestin gene. Case presentation: A 5-year-old Syrian female complains of stationary night blindness, investigated by fundus photo and optical coherence photograph and diagnosed as Oguchi disease. Discussion: Oguchi disease is an autosomal recessive retinal disorder causing stationary nyctalopia. It is characterized by Mizuo-Nakamura phenomenon, which is the alteration of fundus reflex color from golden-yellow to normal with dark adaptation. Literature reports suggest that mutations in rhodopsin kinase or arrestin genes may cause Oguchi's disease. Conclusions: Optical coherence tomography is of great importance in Oguchi's disease. Optical coherence tomography usually shows an absence of the inner and outer segments line in the extrafoveal area during a partly dark-adaptation phase.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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.1388 T > C (p. L463P) were detected. CONCLUSIONS: 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.

X-linked juvenile retinoschisis presenting with rhegmatogenous retinal detachment in a male Nigerian adolescent: A case report.

A 15-year-old boy came to the eye clinic with reduced vision in the left eye of a year's duration and prior trauma. Best-corrected visual acuity was 6/9 and hand movement in both eyes, respectively. The anterior segment examination was essentially normal except for a Marcus Gunn pupil and a polar cataract in the left eye. Goldmann applanation tonometry was 10 and 06 mmHg, respectively, in the right and left eyes. Binocular indirect ophthalmoscopy of the right eye revealed pink disc, normal vessels and the Mizuo-Nakamura phenomenon with a cartwheel appearance at the macula. The left eye had a total retinal detachment with proliferative vitreoretinopathy and retinal tear at 12 o' clock. Optical coherence tomography revealed posterior vitreous detachment and schitic cavities at the macula in the left eye. A diagnosis of left rhegmatogenous retinal detachment with background X-linked juvenile retinoschisis was made. The patient was advised on a pars plana vitrectomy under guarded visual prognosis.

Mizuo-Nakamura phenomenon in X-linked retinoschisis.

Purpose: To 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). Methods: We 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. Results: The 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 Importance: The 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.

A compound heterozygous mutation in the S-Antigen Visual Arrestin SAG gene in a Chinese patient with Oguchi type one: a case report.

BACKGROUND: Oguchi disease is a rare autosomal recessive form of congenital quiescent night blindness. Oguchi disease has been found to be associated with gene mutations in SAG and GRK1, which are vital factors in the recovery phase of phototransduction after light stimuli. We report a case of Oguchi disease with novel heterozygous mutations in SAG. CASE PRESENTATION: A 7-year-old girl with a history of night blindness since childhood, was referred to our hospital. Ophthalmologic examinations included visual acuity, fundus examinations, fundus photography, spectral-domain optical coherence tomography, electroretinographic (ERG). Mutation screening of the SAG and GRK1 genes was performed. This patient exhibited typical clinical characteristics of Oguchi disease, including night blindness, golden fundus with the Mizuo-Nakamura phenomenon, packed structure of the parafovea in optical coherence tomography and reduced a-waves and b-waves in scotopic 3.0 ERG. Genetic testing revealed a heterozygous change in nucleotide c.72_75+15delATCGGTGAGTGGTGCACAA in exon 2 of the SAG gene in this patient, her unaffected mother and younger brother. A splicing alteration of nucleotide c.376-2A>C was identified in exon 6 of the SAG gene with heterozygous status in this patient and her unaffected father. CONCLUSIONS: Compound heterozygosity of a nonsense p.S25X mutation in exon 2 and a splicing alteration in exon 6 of the SAG gene is the cause of this patient with Oguchi type 1 disease in China.

Two novel compound heterozygous SAG mutations in an Italian patient with Oguchi disease: A genetic and multimodal retinal imaging study.

BACKGROUND: Oguchi disease is a rare autosomal recessive retinal dystrophy, characterized by congenital stationary blindness and caused by pathogenic variants in SAG and GRK1 genes. The present study aimed to report an Italian patient affected by Oguchi disease, evaluated by means of a multimodal retinal imaging study and harboring two novel heterozygous pathogenic variants in the SAG gene. MATERIALS AND METHODS: A 60-year-old female complaining congenital stationary night blindness was investigated through fundus photograph, optical coherence tomography (OCT), electroretinography (ERG), and genetic testing. RESULTS: Fundus examination showed a golden-grayish fundus aspect. The rod response of the scotopic ERG was undetectable and mixed rod-cone response was electronegative. Fundus photographs obtained in light and in prolonged dark-adapted conditions allowed to detect the Mizuo-Nakamura phenomenon. Light condition OCT over the abnormal retinal regions showed high-intensity areas in the outer photoreceptor segment layer, that reduced with prolonged dark adaption. Genetic testing identified two rare heterozygous sequence variants in the SAG gene: NM_000541.5:c.807delA p.(Glu270Lysfs*9) and NM_000541.5:c.1047-1G>C confirming the diagnosis of Oguchi disease. CONCLUSIONS: We identified the first Italian compound heterozygous patient harboring two novel alterations in the SAG gene (a frameshift deletion and a splicing variant). The involvement of the SAG gene in Oguchi disease is a common finding in Japanese population, but rarely identified in Caucasians. Clinical suspicion should prompt the molecular analysis of genes associated with this condition.

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.

Wide-field true-colour imaging and clinical characterization of a novel GRK1 mutation in Oguchi disease.

PURPOSE: The available literature regarding Oguchi disease is limited, with around 50 cases described to date. Caused by mutations to either the SAG gene coding for arrestin (Hayashi et al. in Ophthalmic Res 46:175-180, 2011) or the GRK1 gene coding for rhodopsin kinase (Yamamoto et al. in Nat Genet 15:175-178. https://doi.org/10.1038/ng0297-175 , 1997), Oguchi disease is an autosomal recessive condition with a good visual prognosis. The clinical diagnosis of the condition is based on the presence of night blindness (nyctalopia), as well as fundoscopic observation of the Mizuo-Nakamura phenomenon. The Mizuo-Nakamura phenomenon refers to a fundus discolouration described as a golden-brown colour with a yellow-grey metallic sheen most prominent in the peripheral retina; after prolonged dark adaptation, the fundus appears normal. The prevalence of Oguchi disease is highest in Japan, particularly with SAG mutations (Nakazawa et al. in Retina 17:17-22, 1997), although patients from Europe, Pakistan and India have also been described. Formal diagnosis requires genetic testing. METHODS: Wide-field fundus images were obtained in both dark-adapted and light-adapted retina. Optical coherence tomography and dark-adapted electroretinography responses were used to further characterize the clinical phenotype. RESULTS: Existing descriptions of Oguchi disease have been limited by available technology. The flashes required for 45°-montage photographs in a dark-adapted eye quickly cause light adaptation. Recent advances in technology enable the capture of larger retinal areas in a single image. Wide-field 133° images were obtained of the native and dark-adapted fundus in natural colour. To our knowledge, these represent the first reported single-wide-field images of Oguchi disease, showing the characteristic Mizuo-Nakamura phenomenon in true colour. Genetic testing revealed a novel homozygous mutation in GRK1. CONCLUSIONS: Here, we demonstrate how characterizing this condition with single-shot true-colour wide-field imaging has distinct advantages over scanning laser technology, which applies artificial colouration, or stitched true-colour images. Images captured with wide-field systems create a much better representation of the native and dark-adapted fundus than can be observed by the ophthalmologist using direct fundoscopy and are essential in the clinical characterization of new mutations.

Alterações eletrofisiológicas na doença de Oguchi / Electrophysiological findings in Oguchi disease

Descrever as alterações eletrofuncionais em um caso raríssimo da Doença de Oguchi. Paciente do sexo feminino, italiana de 17 anos de idade se queixava de cegueira noturna. A resposta escotópica de bastonetes, do ERG era não registrável. A resposta escotópica ao estímulo branco forte demonstrava uma diminuição de amplitude da onda B. As respostas ao flicker de 30Hz e ao EOG eram dentro dos limites da normalidade. Era presente o fenômeno de Mizuo-Nakamura. Os exames eletrofuncionais são muito importantes no diagnóstico de certeza da doença de Oguchi. É nítida, no presente caso, a discordância entre EOG e ERG. Considerando a função dos bastonetes, as respostas normais do EOG contrastam com a ausência de respostas dos bastonetes em condições escotópicas no ERG. Mais estudos são necessários para entender o complexo mecanismo eletrofuncional dessa doença e melhor definir a origem dos componentes sensíveis à luz do EOG...

To describe the electrophysiological alterations in a very rare case of Oguchi's disease. A 17-year-old italian girl complaining of night blindness underwent complete ophthalmological exams, including electrophysiological tests. Rod responses were nondetectable in full-field electroretinogram (ERG). The photopic ERG funtions, including the 30 Hz flicker ERG response was normal, while the scotopic b-wave was diminished in amplitude. The electrooculography (EOG) ratios within the normal range were 208% in the right eye and 222% in the left eye. The Mizuo-Nakamura phenomenon was present. The electrophysiological tests are important tools in Oguchi's disease diagnosis. In the present case, it's clear the non correspondance between EOG and ERG. Considering the rod function, the normal EOG ratio contrast with non-detectable rod ERG responses. More studies are necessary to understand the compless electrofuntional mecanism of the disease helping to understand the origin of the light-sensitive component of the EOG...

Specific Spectral Domain Optical Coherence Tomographic Findings of Oguchi Disease

PURPOSE: To report specific spectral domain OCT findings of Oguchi disease diagnosed with fundoscopic examination and electrophysiological study. CASE SUMMARY: A 14-year-old patient visited our clinic with a complaint of night blindness for ten years. Fundoscopic examination showed a golden-yellow fundus reflex. After three hours of dark adaptation, the fundus color returned to normal (Mizuo-Nakamura phenomenon). In full-field ERG, rod b-wave was not detectable. The a-wave amplitude in maximal combined response increased after three hours of dark adaptation, although the b-wave amplitude was similar to the amplitude before dark adaptation, demonstrating a negative waveform. In the spectral domain OCT images of the perifoveal area, no gap between the retinal pigment epithelium and the inner segment/outer segment (IS/OS) junction was detected before prolonged dark adaptation, and a highly reflective band was shown. However, the gap appeared after three hours of dark adaptation, and two highly reflective bands were detected in the OCT images. CONCLUSIONS: The characteristic OCT finding in addition to the specific fundoscopic finding and full-field ERG results may be useful to diagnose Oguchi disease.