Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients
Leber’s hereditary optic neuropathy (LHON) is a rare maternally inherited disease caused by mutations in mitochondrial DNA (mtDNA) genes encoding subunits of complex I in the mitochondrial respiratory chain. The most common mutations causing LHON are G11778A, G3460A and T14484C, but there are also s...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-03-01
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| Series: | Biotechnology & Biotechnological Equipment |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13102818.2023.2255073 |
| _version_ | 1826964081970511872 |
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| author | Sylvia Cherninkova Boryana Zaharova Kunka Kamenarova Kalina Mihova Slavena Atemin Tihomir Todorov Vasil Haykin Alexander Oscar Ivailo Tournev Radka Kaneva Albena Todorova |
| author_facet | Sylvia Cherninkova Boryana Zaharova Kunka Kamenarova Kalina Mihova Slavena Atemin Tihomir Todorov Vasil Haykin Alexander Oscar Ivailo Tournev Radka Kaneva Albena Todorova |
| author_sort | Sylvia Cherninkova |
| collection | DOAJ |
| description | Leber’s hereditary optic neuropathy (LHON) is a rare maternally inherited disease caused by mutations in mitochondrial DNA (mtDNA) genes encoding subunits of complex I in the mitochondrial respiratory chain. The most common mutations causing LHON are G11778A, G3460A and T14484C, but there are also several less common mutations. LHON presents as acute or subacute bilateral visual loss, usually affecting young males. The aim of this study was to assess the clinical symptomatology and genetic analysis of Bulgarian patients with LHON. Twenty-two patients were diagnosed with LHON based on clinical evaluation and genetic examination (17 males and 5 females); 12 of them were previously reported, while 8 males and 2 females are newly diagnosed. A full neuroophthalmologic and genetic examination was performed. Eight patients had a family history of LHON, while 14 were isolated cases. The age at onset ranged from 3 to 43 years, and visual acuity ranged from counting fingers to 0.9. Genetic testing revealed various mutations, including a rare mutation G3635A in MT-ND1 in five affected members of one pedigree and digenic inheritance of G11778A and T14484C in three individuals from a different family. A variant m.15988A > G in the mitochondrial gene MT-TP with a high level of heteroplasmy was found in one patient. In addition to the most common mutations causing LHON, our patients also had rare mutations. These results suggest that genetic analysis of the entire mtDNA sequence is recommended in cases with strong clinical suspicion of LHON, since new rare mtDNA pathogenic variants are being identified. |
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| institution | Directory Open Access Journal |
| issn | 1310-2818 1314-3530 |
| language | English |
| last_indexed | 2025-02-18T02:50:18Z |
| publishDate | 2023-03-01 |
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| series | Biotechnology & Biotechnological Equipment |
| spelling | doaj.art-4ca00a1855a9411e9a9c632f17e2074f2024-11-25T09:24:34ZengTaylor & Francis GroupBiotechnology & Biotechnological Equipment1310-28181314-35302023-03-0137110.1080/13102818.2023.2255073Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patientsSylvia Cherninkova0Boryana Zaharova1Kunka Kamenarova2Kalina Mihova3Slavena Atemin4Tihomir Todorov5Vasil Haykin6Alexander Oscar7Ivailo Tournev8Radka Kaneva9Albena Todorova10Clinic of Neurological Diseases, University Hospital “Aleksandrovska”, Medical University of Sofia, Sofia, BulgariaGenetic Medico-Diagnostic Laboratory “Genica”, Sofia, BulgariaGenome Diagnostics Laboratory, Molecular Medicine Center, Medical University of Sofia, Sofia, BulgariaGenome Diagnostics Laboratory, Molecular Medicine Center, Medical University of Sofia, Sofia, BulgariaGenetic Medico-Diagnostic Laboratory “Genica”, Sofia, BulgariaGenetic Medico-Diagnostic Laboratory “Genica”, Sofia, BulgariaClinic of Eye Diseases, University Hospital “Aleksandrovska”, Sofia, BulgariaClinic of Eye Diseases, University Hospital “Aleksandrovska”, Sofia, BulgariaClinic of Neurological Diseases, University Hospital “Aleksandrovska”, Medical University of Sofia, Sofia, BulgariaGenome Diagnostics Laboratory, Molecular Medicine Center, Medical University of Sofia, Sofia, BulgariaGenetic Medico-Diagnostic Laboratory “Genica”, Sofia, BulgariaLeber’s hereditary optic neuropathy (LHON) is a rare maternally inherited disease caused by mutations in mitochondrial DNA (mtDNA) genes encoding subunits of complex I in the mitochondrial respiratory chain. The most common mutations causing LHON are G11778A, G3460A and T14484C, but there are also several less common mutations. LHON presents as acute or subacute bilateral visual loss, usually affecting young males. The aim of this study was to assess the clinical symptomatology and genetic analysis of Bulgarian patients with LHON. Twenty-two patients were diagnosed with LHON based on clinical evaluation and genetic examination (17 males and 5 females); 12 of them were previously reported, while 8 males and 2 females are newly diagnosed. A full neuroophthalmologic and genetic examination was performed. Eight patients had a family history of LHON, while 14 were isolated cases. The age at onset ranged from 3 to 43 years, and visual acuity ranged from counting fingers to 0.9. Genetic testing revealed various mutations, including a rare mutation G3635A in MT-ND1 in five affected members of one pedigree and digenic inheritance of G11778A and T14484C in three individuals from a different family. A variant m.15988A > G in the mitochondrial gene MT-TP with a high level of heteroplasmy was found in one patient. In addition to the most common mutations causing LHON, our patients also had rare mutations. These results suggest that genetic analysis of the entire mtDNA sequence is recommended in cases with strong clinical suspicion of LHON, since new rare mtDNA pathogenic variants are being identified.https://www.tandfonline.com/doi/10.1080/13102818.2023.2255073Leber’s hereditary optic neuropathyneuroophthalmologic examinationgenetic examinationrare mutationmtDNA |
| spellingShingle | Sylvia Cherninkova Boryana Zaharova Kunka Kamenarova Kalina Mihova Slavena Atemin Tihomir Todorov Vasil Haykin Alexander Oscar Ivailo Tournev Radka Kaneva Albena Todorova Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients Biotechnology & Biotechnological Equipment Leber’s hereditary optic neuropathy neuroophthalmologic examination genetic examination rare mutation mtDNA |
| title | Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients |
| title_full | Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients |
| title_fullStr | Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients |
| title_full_unstemmed | Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients |
| title_short | Leber’s hereditary optic neuropathy: clinical and genetic analysis of Bulgarian patients |
| title_sort | leber s hereditary optic neuropathy clinical and genetic analysis of bulgarian patients |
| topic | Leber’s hereditary optic neuropathy neuroophthalmologic examination genetic examination rare mutation mtDNA |
| url | https://www.tandfonline.com/doi/10.1080/13102818.2023.2255073 |
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