Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree
Emperador, Sonia (Universidad de Zaragoza) ; Habbane, Mouna ; López-Gallardo, Ester (Universidad de Zaragoza) ; del Rio, Alejandro ; Llobet, Laura ; Mateo, Javier ; Sanz-López, Ana María ; Fernández-García, María José ; Sánchez-Tocino, Hortensia ; Benbunan-Ferreiro, Sol ; Calabuig-Goena, María ; Narvaez-Palazón, Carlos ; Fernández-Vega, Beatriz ; González-Iglesias, Hector ; Urreizti, Roser ; Artuch, Rafael ; Pacheu-Grau, David (Universidad de Zaragoza) ; Bayona-Bafaluy, Pilar (Universidad de Zaragoza) ; Montoya, Julio (Universidad de Zaragoza) ; Ruiz-Pesini, Eduardo (Universidad de Zaragoza)
Resumen: 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.
Idioma: Inglés
DOI: 10.1186/s13023-024-03165-2
Año: 2024
Publicado en: Orphanet Journal of Rare Diseases 19, 1 (2024), 148 [10 pp.]
ISSN: 1750-1172
Factor impacto JCR: 3.5 (2024)
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 68 / 195 = 0.349 (2024) - Q2 - T2
Categ. JCR: GENETICS & HEREDITY rank: 61 / 191 = 0.319 (2024) - Q2 - T1
Factor impacto SCIMAGO: 1.269 - Genetics (clinical) (Q1) - Pharmacology (medical) (Q1) - Medicine (miscellaneous) (Q1)
Tipo y forma: Artículo (Versión definitiva)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
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Exportado de SIDERAL (2025-09-22-14:35:46)
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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.
Idioma: Inglés
DOI: 10.1186/s13023-024-03165-2
Año: 2024
Publicado en: Orphanet Journal of Rare Diseases 19, 1 (2024), 148 [10 pp.]
ISSN: 1750-1172
Factor impacto JCR: 3.5 (2024)
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 68 / 195 = 0.349 (2024) - Q2 - T2
Categ. JCR: GENETICS & HEREDITY rank: 61 / 191 = 0.319 (2024) - Q2 - T1
Factor impacto SCIMAGO: 1.269 - Genetics (clinical) (Q1) - Pharmacology (medical) (Q1) - Medicine (miscellaneous) (Q1)
Tipo y forma: Artículo (Versión definitiva)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Debe reconocer adecuadamente la autoría, proporcionar un enlace a la licencia e indicar si se han realizado cambios. Puede hacerlo de cualquier manera razonable, pero no de una manera que sugiera que tiene el apoyo del licenciador o lo recibe por el uso que hace. Exportado de SIDERAL (2025-09-22-14:35:46)
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Este artículo se encuentra en las siguientes colecciones:
Artículos > Artículos por área > Bioquímica y Biología Molecular
Artículos > Artículos por área > Histología
Registro creado el 2024-04-24, última modificación el 2025-09-23