Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree
Abstract Background Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The rema...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-024-03165-2 |
| _version_ | 1827291332469587968 |
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| author | Sonia Emperador Mouna Habbane Ester López-Gallardo Alejandro del Rio Laura Llobet Javier Mateo Ana María Sanz-López María José Fernández-García Hortensia Sánchez-Tocino Sol Benbunan-Ferreiro María Calabuig-Goena Carlos Narvaez-Palazón Beatriz Fernández-Vega Hector González-Iglesias Roser Urreizti Rafael Artuch David Pacheu-Grau Pilar Bayona-Bafaluy Julio Montoya Eduardo Ruiz-Pesini |
| author_facet | Sonia Emperador Mouna Habbane Ester López-Gallardo Alejandro del Rio Laura Llobet Javier Mateo Ana María Sanz-López María José Fernández-García Hortensia Sánchez-Tocino Sol Benbunan-Ferreiro María Calabuig-Goena Carlos Narvaez-Palazón Beatriz Fernández-Vega Hector González-Iglesias Roser Urreizti Rafael Artuch David Pacheu-Grau Pilar Bayona-Bafaluy Julio Montoya Eduardo Ruiz-Pesini |
| author_sort | Sonia Emperador |
| collection | DOAJ |
| description | Abstract Background Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. Results We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. Conclusions With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance. |
| first_indexed | 2024-04-24T12:36:12Z |
| format | Article |
| id | doaj.art-6e3b9de78c4e4071ad94d231642e4ed6 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-24T12:36:12Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-6e3b9de78c4e4071ad94d231642e4ed62024-04-07T11:30:39ZengBMCOrphanet Journal of Rare Diseases1750-11722024-04-0119111010.1186/s13023-024-03165-2Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigreeSonia Emperador0Mouna Habbane1Ester López-Gallardo2Alejandro del Rio3Laura Llobet4Javier Mateo5Ana María Sanz-López6María José Fernández-García7Hortensia Sánchez-Tocino8Sol Benbunan-Ferreiro9María Calabuig-Goena10Carlos Narvaez-Palazón11Beatriz Fernández-Vega12Hector González-Iglesias13Roser Urreizti14Rafael Artuch15David Pacheu-Grau16Pilar Bayona-Bafaluy17Julio Montoya18Eduardo Ruiz-Pesini19Departamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaServicio de Oftalmología, Hospital Clínico Universitario Lozano BlesaServicio de Oftalmología, Hospital Universitario de ToledoServicio de Oftalmología, Hospital Universitario de ToledoServicio de Oftalmología. Hospital Universitario Río HortegaServicio de Oftalmología. Hospital Universitario Río HortegaServicio de Oftalmología. Hospital Universitario Río HortegaInstituto Oftalmológico RecoletasInstituto Oftalmológico Fernández-VegaInstituto de Productos Lácteos de Asturias, Consejo Superior de Investigaciones Científicas (IPLA-CSIC)Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos IIICentro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos IIIDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaDepartamento de Bioquímica, Biología Molecular y Celular, Universidad de ZaragozaAbstract Background Most patients suffering from Leber hereditary optic neuropathy carry one of the three classic pathologic mutations, but not all individuals with these genetic alterations develop the disease. There are different risk factors that modify the penetrance of these mutations. The remaining patients carry one of a set of very rare genetic variants and, it appears that, some of the risk factors that modify the penetrance of the classical pathologic mutations may also affect the phenotype of these other rare mutations. Results We describe a large family including 95 maternally related individuals, showing 30 patients with Leber hereditary optic neuropathy. The mutation responsible for the phenotype is a novel transition, m.3734A > G, in the mitochondrial gene encoding the ND1 subunit of respiratory complex I. Molecular-genetic, biochemical and cellular studies corroborate the pathogenicity of this genetic change. Conclusions With the study of this family, we confirm that, also for this very rare mutation, sex and age are important factors modifying penetrance. Moreover, this pedigree offers an excellent opportunity to search for other genetic or environmental factors that additionally contribute to modify penetrance.https://doi.org/10.1186/s13023-024-03165-2Leber hereditary optic neuropathyMitochondrial DNAPathologic mutationLarge pedigreeIncomplete penetrance |
| spellingShingle | Sonia Emperador Mouna Habbane Ester López-Gallardo Alejandro del Rio Laura Llobet Javier Mateo Ana María Sanz-López María José Fernández-García Hortensia Sánchez-Tocino Sol Benbunan-Ferreiro María Calabuig-Goena Carlos Narvaez-Palazón Beatriz Fernández-Vega Hector González-Iglesias Roser Urreizti Rafael Artuch David Pacheu-Grau Pilar Bayona-Bafaluy Julio Montoya Eduardo Ruiz-Pesini Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree Orphanet Journal of Rare Diseases Leber hereditary optic neuropathy Mitochondrial DNA Pathologic mutation Large pedigree Incomplete penetrance |
| title | Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree |
| title_full | Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree |
| title_fullStr | Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree |
| title_full_unstemmed | Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree |
| title_short | Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree |
| title_sort | identification and characterization of a new pathologic mutation in a large leber hereditary optic neuropathy pedigree |
| topic | Leber hereditary optic neuropathy Mitochondrial DNA Pathologic mutation Large pedigree Incomplete penetrance |
| url | https://doi.org/10.1186/s13023-024-03165-2 |
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