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Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease
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 as...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103117/ https://www.ncbi.nlm.nih.gov/pubmed/35549688 http://dx.doi.org/10.1186/s12886-022-02444-5 |
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author | Tawfik, Caroline Atef Elbagoury, Nagham Maher Khater, Noha Ibrahim Essawi, Mona Lotfi |
author_facet | Tawfik, Caroline Atef Elbagoury, Nagham Maher Khater, Noha Ibrahim Essawi, Mona Lotfi |
author_sort | Tawfik, Caroline Atef |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9103117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91031172022-05-14 Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease Tawfik, Caroline Atef Elbagoury, Nagham Maher Khater, Noha Ibrahim Essawi, Mona Lotfi BMC Ophthalmol Research 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. BioMed Central 2022-05-12 /pmc/articles/PMC9103117/ /pubmed/35549688 http://dx.doi.org/10.1186/s12886-022-02444-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Tawfik, Caroline Atef Elbagoury, Nagham Maher Khater, Noha Ibrahim Essawi, Mona Lotfi Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease |
title | Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease |
title_full | Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease |
title_fullStr | Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease |
title_full_unstemmed | Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease |
title_short | Mutation analysis reveals novel and known mutations in SAG gene in first two Egyptian families with Oguchi disease |
title_sort | mutation analysis reveals novel and known mutations in sag gene in first two egyptian families with oguchi disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103117/ https://www.ncbi.nlm.nih.gov/pubmed/35549688 http://dx.doi.org/10.1186/s12886-022-02444-5 |
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