Pierron Denis, Ferré Marc, Rocher Christophe, Chevrollier Arnaud, Murail Pascal, Thoraval Didier, Amati-Bonneau Patrizia, Reynier Pascal, Letellier Thierry
Université Bordeaux 1, Laboratoire d'Anthropologie des Populations du Passé, UMR 5199 PACEA, 33400 Talence, France.
BMC Med Genet. 2009 Jul 20;10:70. doi: 10.1186/1471-2350-10-70.
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.
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.
The comparison between patient and reference populations did not revealed any significant difference.
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).
Leber遗传性视神经病变（LHON）和常染色体显性视神经萎缩（ADOA）是遗传性视神经病变最常见的形式。LHON与线粒体DNA（mtDNA）突变相关，而ADOA主要是由于OPA1基因突变所致，该基因编码一种参与线粒体内膜重塑的线粒体蛋白。已证实mtDNA单倍群J对LHON表达有显著影响，最近有人提出该单倍群也可能影响ADOA表达。在本研究中，我们测试了mtDNA背景对OPA1突变的影响。
为了确定OPA1突变与mtDNA背景之间的关系，我们通过对41例受OPA1相关ADOA影响的法国患者的线粒体DNA进行控制区测序和限制性片段长度多态性（RFLP）检测，确定其单倍群归属。
患者群体与参考群体之间的比较未发现任何显著差异。
我们的结果表明mtDNA背景对ADOA表达没有强烈影响。这些数据表明，OPA1可被视为直接导致视神经萎缩的“严重突变”，而OPA1阴性的ADOA和LHON突变需要外部因素来表达病变（即与线粒体背景协同相互作用）。
