A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy
Abstract Background Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by homozygous or compound heterozygous null variants in the BEST1 gene. Clinically, ARB presents with variable features including central visual impairment, global photoreceptor dysfunction (as indicate...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-025-03813-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850141343732465664 |
|---|---|
| author | Nagham Maher Elbagoury Caroline Atef Tawfik Asmaa Fawzy Abdel-Aleem Heba Mahmoud Fathy Dina Nabil Baddar Mona Lotfi Essawi |
| author_facet | Nagham Maher Elbagoury Caroline Atef Tawfik Asmaa Fawzy Abdel-Aleem Heba Mahmoud Fathy Dina Nabil Baddar Mona Lotfi Essawi |
| author_sort | Nagham Maher Elbagoury |
| collection | DOAJ |
| description | Abstract Background Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by homozygous or compound heterozygous null variants in the BEST1 gene. Clinically, ARB presents with variable features including central visual impairment, global photoreceptor dysfunction (as indicated by abnormal full-field ERG), and a significantly reduced electro-oculogram (EOG) light rise, a hallmark of bestrophinopathy. Fundus examination reveals widespread retinal pigment epithelial (RPE) disturbance, vitelliform deposits in the posterior pole (more clearly visualized with fundus autofluorescence), and macular fluid accumulation. Angle-closure glaucoma, secondary to anterior chamber dysgenesis, is a potential complication. This work aims at documenting the founder effect of a novel variant in the BEST1 gene causing autosomal recessive bestrophinopathy and determining its variable clinical features. Methods Twelve members of nine unrelated, consanguineous Egyptian families with a history of impaired central vision underwent comprehensive ophthalmological examination, fundus color photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) of the macula, and electrophysiological studies. Variant screening of coding exons of the BEST1 gene and some flanking regions was performed using the Sanger sequencing technique. The pathogenicity of the variants was tested using different in silico functional analysis tools. Results The clinical examination and investigations confirmed the ARB phenotype. All twelve patients exhibited (c.365 G > C, p. Arg122Pro) a novel BEST1 gene variant in a homozygous form. On top of the classical retinal phenotype of ARB, some patients had other ocular associations: four patients were found to have angle-closure glaucoma, one patient had associated corneal dystrophy, one developed a macular hole, and one patient developed uveitis. Conclusion The identification of the same, novel homozygous BEST1 missense variant in twelve patients from nine unrelated, consanguineous families of Egyptian origin, suggests a founder effect. Angle-closure glaucoma was the most commonly associated ocular abnormality (30%). Our finding expands the molecular spectrum of ARB-associated variants, and identification of this founder variant can simplify genetic testing in the presence of limited resources and lead to better counseling. |
| format | Article |
| id | doaj-art-b0602d6531b544de90db32d4faf62c5f |
| institution | OA Journals |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-b0602d6531b544de90db32d4faf62c5f2025-08-20T02:29:27ZengBMCOrphanet Journal of Rare Diseases1750-11722025-05-0120111110.1186/s13023-025-03813-1A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathyNagham Maher Elbagoury0Caroline Atef Tawfik1Asmaa Fawzy Abdel-Aleem2Heba Mahmoud Fathy3Dina Nabil Baddar4Mona Lotfi Essawi5Department of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research CentreDepartment of Ophthalmology, Ain Shams UniversityDepartment of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research CentreDepartment of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research CentreWatany Eye HospitalDepartment of Medical Molecular Genetics, Human Genetics and Genome Research Institute, National Research CentreAbstract Background Autosomal recessive bestrophinopathy (ARB) is a rare retinal dystrophy caused by homozygous or compound heterozygous null variants in the BEST1 gene. Clinically, ARB presents with variable features including central visual impairment, global photoreceptor dysfunction (as indicated by abnormal full-field ERG), and a significantly reduced electro-oculogram (EOG) light rise, a hallmark of bestrophinopathy. Fundus examination reveals widespread retinal pigment epithelial (RPE) disturbance, vitelliform deposits in the posterior pole (more clearly visualized with fundus autofluorescence), and macular fluid accumulation. Angle-closure glaucoma, secondary to anterior chamber dysgenesis, is a potential complication. This work aims at documenting the founder effect of a novel variant in the BEST1 gene causing autosomal recessive bestrophinopathy and determining its variable clinical features. Methods Twelve members of nine unrelated, consanguineous Egyptian families with a history of impaired central vision underwent comprehensive ophthalmological examination, fundus color photography, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) of the macula, and electrophysiological studies. Variant screening of coding exons of the BEST1 gene and some flanking regions was performed using the Sanger sequencing technique. The pathogenicity of the variants was tested using different in silico functional analysis tools. Results The clinical examination and investigations confirmed the ARB phenotype. All twelve patients exhibited (c.365 G > C, p. Arg122Pro) a novel BEST1 gene variant in a homozygous form. On top of the classical retinal phenotype of ARB, some patients had other ocular associations: four patients were found to have angle-closure glaucoma, one patient had associated corneal dystrophy, one developed a macular hole, and one patient developed uveitis. Conclusion The identification of the same, novel homozygous BEST1 missense variant in twelve patients from nine unrelated, consanguineous families of Egyptian origin, suggests a founder effect. Angle-closure glaucoma was the most commonly associated ocular abnormality (30%). Our finding expands the molecular spectrum of ARB-associated variants, and identification of this founder variant can simplify genetic testing in the presence of limited resources and lead to better counseling.https://doi.org/10.1186/s13023-025-03813-1AfricaAutosomal recessive bestrophinopathyBEST1 geneEgyptFounder effectMissense variant |
| spellingShingle | Nagham Maher Elbagoury Caroline Atef Tawfik Asmaa Fawzy Abdel-Aleem Heba Mahmoud Fathy Dina Nabil Baddar Mona Lotfi Essawi A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy Orphanet Journal of Rare Diseases Africa Autosomal recessive bestrophinopathy BEST1 gene Egypt Founder effect Missense variant |
| title | A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy |
| title_full | A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy |
| title_fullStr | A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy |
| title_full_unstemmed | A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy |
| title_short | A novel founder variant in BEST1 gene causing autosomal recessive bestrophinopathy |
| title_sort | novel founder variant in best1 gene causing autosomal recessive bestrophinopathy |
| topic | Africa Autosomal recessive bestrophinopathy BEST1 gene Egypt Founder effect Missense variant |
| url | https://doi.org/10.1186/s13023-025-03813-1 |
| work_keys_str_mv | AT naghammaherelbagoury anovelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT carolineateftawfik anovelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT asmaafawzyabdelaleem anovelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT hebamahmoudfathy anovelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT dinanabilbaddar anovelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT monalotfiessawi anovelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT naghammaherelbagoury novelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT carolineateftawfik novelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT asmaafawzyabdelaleem novelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT hebamahmoudfathy novelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT dinanabilbaddar novelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy AT monalotfiessawi novelfoundervariantinbest1genecausingautosomalrecessivebestrophinopathy |