2024-03-28T13:57:26Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1510632019-10-23T12:56:39Zcom_10261_22com_10261_1col_10261_275
00925njm 22002777a 4500
dc
Cruz-Bermúdez, Alberto
author
Vicente-Blanco, Ramiro J.
author
Hernández-Sierra, Rosana
author
Blázquez, Alberto
author
Martín, Miguel A.
author
Garesse, Rafael
author
Fernández-Moreno, Miguel Ángel
author
2016
The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations.
PLoS ONE 11(1): e0146816 (2016)
http://hdl.handle.net/10261/151063
10.1371/journal.pone.0146816
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/100012818
26784702
Functional characterization of three concomitant MtDNA LHON mutations shows no synergistic effect on mitochondrial activity