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

Colombo, Leonardo; Abeshi, Andi; Maltese, Paolo Enrico; Frecer, Vladimı́r; Miertuš, Ján; Cerra, Davide; Bertelli, Matteo; Rossetti, Luca

doi:10.1016/j.ejmg.2018.09.015

Cited by 5 publications

(8 citation statements)

References 18 publications

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“…7,11 Apart from few exceptions, SAG mutational spectrum reported so far includes predominantly null variants (nonsense, frameshift, or gross deletions). 7,8,12 Recently, a splicing alteration in the SAG gene has been described in a Chinese patient with Oguchi Disease associated with Multiple Evanescent White Dot Syndrome (MEWDS). 13 Furthermore, most patients were found to be homozygous because of consanguinity and/or the presence of common founder mutations, as for the c.924delA deletion (previously termed 1147delA) in Japan.…”

Section: Discussionmentioning

confidence: 99%

“…7,8 To date, only two Italian patients with Oguchi disease have been reported in the literature: the first harbored the homozygous variant c.470T>C (p.Leu157Pro) in the GRK1 gene, whereas the homozygous missense substitution NM_000541:c.398C>T p.(Ser133Leu) in the SAG gene was found in the second family. 7,11 Apart from few exceptions, SAG mutational spectrum reported so far includes predominantly null variants (nonsense, frameshift, or gross deletions). 7,8,12 Recently, a splicing alteration in the SAG gene has been described in a Chinese patient with Oguchi Disease associated with Multiple Evanescent White Dot Syndrome (MEWDS).…”

Section: Discussionmentioning

confidence: 99%

“…Pathogenic variants in SAG (Oguchi type 1) and GRK1 (Oguchi type 2) genes, which encode proteins that plays an essential role in inactivating photoactivated rhodopsin, have been identified in Oguchi disease patients, resulting in marked rod dysfunction and delaying recovery of rod sensitivity. 3,7,8 Biallelic mutations in the SAG gene have been associated not only with Oguchi type 1, but also with autosomal recessive retinitis pigmentosa (RP47, MIM # 613758) and Eales disease. 7,9 Moreover, the heterozygous missense substitution c.440G>T p.(Cys147Phe) in the SAG gene was reported in twelve families of Hispanic origin affected by an autosomal dominant retinitis pigmentosa without the clinical features of Oguchi disease.…”

Section: Discussionmentioning

confidence: 99%

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

Pilotto

Trevisson

Nacci

et al. 2021

European Journal of Ophthalmology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Pilotto

Trevisson

Nacci

et al. 2021

European Journal of Ophthalmology

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show abstract

“…Based on mutations in these two genes, the Oguchi disease is divided into 2 categories. Oguchi disease-1 is caused by homozygous or heterozygous mutations in the SAG gene, which is located on chromosome 2q37.1 [ 2 , 7 , 8 ]. The S-antigen forms a compound with photoactivated-phosphorylated rhodopsin, preventing further interaction with activated rhodopsin, thus making it an important factor in the phototransduction recovery stage.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Oguchi disease has been demonstrated to be more prevalent among the Japanese population as compared to other populations [1]. To the authors' knowledge, around 50 cases of Oguchi disease have been reported worldwide and those have been primarily concentrated in Japan with few reported cases from Europe [10][11][12][13], Turkey [14], China [15], India [16], Pakistan [17,18] and Iran [19].…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease

et al. 2022

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Background Oguchi disease is a rare type of congenital stationary night blindness associated with an abnormal fundus appearance. It is inherited in an autosomal recessive manner where two types exist according to the gene affected; type 1 associated with S-antigen (SAG) gene mutations and type 2 associated with rhodopsin kinase (GRK1) gene mutations. Purpose The aim of this work was to describe the clinical and genetic findings of the first two reported families of Oguchi disease in Egypt and African region. Methods Four members of two consanguineous Egyptian families with history of night blindness since childhood underwent complete ophthalmological examination, standard automated static perimetry, fundus color photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) in light-adapted state and spectral-domain optical coherence tomography (SD-OCT) of both the macula and the optic nerve head as well as central corneal thickness with repeated fundus photography following prolonged dark adaptation. Mutation screening of 7 coding exons of GRK1 gene and 15 coding exons of SAG gene as well as some flanking regions were performed using Sanger sequencing technique. The variants were tested for pathogenicity using different in silico functional analysis tools. Results The clinical examination and investigations confirmed Oguchi disease phenotype. One patient showed p.R193* (c.577C > T) which is a previously reported SAG gene mutation in a homozygous form. The other three patients from a different family showed (c.649–1 G > C), a novel canonical splice site SAG gene mutation in a homozygous form. Conclusion The identification of the novel canonical splice site SAG gene variant in three members of the same family with clinically confirmed Oguchi disease reinforces its pathogenicity. A fourth patient from another family carried a previously reported mutation in the same gene. SAG gene variants may be the underlying genetic cause for Oguchi disease in Egypt. Our findings have expanded the spectrum of Oguchi disease-associated mutations in SAG gene and may serve as a basis for genetic diagnosis for Oguchi disease.

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

Cited by 5 publications

References 18 publications

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

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

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

Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease

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