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OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background
BACKGROUND: Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mi...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726129/ https://www.ncbi.nlm.nih.gov/pubmed/19619285 http://dx.doi.org/10.1186/1471-2350-10-70 |
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author | Pierron, Denis Ferré, Marc Rocher, Christophe Chevrollier, Arnaud Murail, Pascal Thoraval, Didier Amati-Bonneau, Patrizia Reynier, Pascal Letellier, Thierry |
author_facet | Pierron, Denis Ferré, Marc Rocher, Christophe Chevrollier, Arnaud Murail, Pascal Thoraval, Didier Amati-Bonneau, Patrizia Reynier, Pascal Letellier, Thierry |
author_sort | Pierron, Denis |
collection | PubMed |
description | BACKGROUND: Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations. METHODS: To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs. RESULTS: The comparison between patient and reference populations did not revealed any significant difference. CONCLUSION: Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s) to express the pathology (i.e. synergistic interaction with mitochondrial background). |
format | Text |
id | pubmed-2726129 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-27261292009-08-13 OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background Pierron, Denis Ferré, Marc Rocher, Christophe Chevrollier, Arnaud Murail, Pascal Thoraval, Didier Amati-Bonneau, Patrizia Reynier, Pascal Letellier, Thierry BMC Med Genet Research Article BACKGROUND: Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations. METHODS: To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs. RESULTS: The comparison between patient and reference populations did not revealed any significant difference. CONCLUSION: Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s) to express the pathology (i.e. synergistic interaction with mitochondrial background). BioMed Central 2009-07-20 /pmc/articles/PMC2726129/ /pubmed/19619285 http://dx.doi.org/10.1186/1471-2350-10-70 Text en Copyright © 2009 Pierron et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Pierron, Denis Ferré, Marc Rocher, Christophe Chevrollier, Arnaud Murail, Pascal Thoraval, Didier Amati-Bonneau, Patrizia Reynier, Pascal Letellier, Thierry OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background |
title | OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background |
title_full | OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background |
title_fullStr | OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background |
title_full_unstemmed | OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background |
title_short | OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background |
title_sort | opa1-related dominant optic atrophy is not strongly influenced by mitochondrial dna background |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726129/ https://www.ncbi.nlm.nih.gov/pubmed/19619285 http://dx.doi.org/10.1186/1471-2350-10-70 |
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