134536 20260217205450.0 doi 10.1186/s13023-024-03165-2 sideral 138192 ART-2024-138192 eng Emperador, Sonia Universidad de Zaragoza (orcid)0000-0001-5964-6138 Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree 2024 Access copy available to the general public Unrestricted 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. info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 3.5 2024 MEDICINE, RESEARCH & EXPERIMENTAL 68 / 195 = 0.349 2024 Q2 T2 GENETICS & HEREDITY 61 / 192 = 0.318 2024 Q2 T1 1.269 2024 Genetics (clinical) 2024 Q1 Pharmacology (medical) 2024 Q1 Medicine (miscellaneous) 2024 Q1 6.2 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Habbane, Mouna López-Gallardo, Ester Universidad de Zaragoza (orcid)0000-0002-3217-1424 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 (orcid)0000-0003-2645-3983 Bayona-Bafaluy, Pilar Universidad de Zaragoza (orcid)0000-0002-8585-6371 Montoya, Julio Universidad de Zaragoza (orcid)0000-0003-1770-6299 Ruiz-Pesini, Eduardo Universidad de Zaragoza (orcid)0000-0002-0269-7337 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 19, 1 (2024), 148 [10 pp.] Orphanet j. rare dis. Orphanet Journal of Rare Diseases 1750-1172 1307358 http://zaguan.unizar.es/record/134536/files/texto_completo.pdf Versión publicada 2267121 http://zaguan.unizar.es/record/134536/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:134536 articulos driver 2026-02-17-20:18:50 ARTICLE