Munakata Kae, Fujii Kumiko, Nanko Shinichiro, Kunugi Hiroshi, Kato Tadafumi
Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, Saitama 351-0198, Japan.
Mutat Res. 2007 Apr 1;617(1-2):119-24. doi: 10.1016/j.mrfmmm.2007.01.006. Epub 2007 Jan 21.
Recent studies suggest that mutations/polymorphisms of mitochondrial DNA (mtDNA) are associated with neuropsychiatric diseases. We identified a patient with major depression and epilepsy. Some family members in the pedigree of the proband had bipolar disorder, depression, suicide, or psychotic disorder not otherwise specified. The mode of inheritance was compatible with maternal inheritance with low penetration. We assumed that the mental disorder in this family might be associated with maternally inherited mitochondrial DNA (mtDNA) mutation. We sequenced the entire mtDNA of the proband. Among the 34 base substitutions detected in the proband, two homoplasmic, nonsynonymous single substitutions of mtDNA, T3394C in MT-ND1 and A9115G in MT-ATP6, were suspected to cause functional impairment, because the former was reported to be disease-related and the latter is vary rare. To study the functional outcome of these substitutions, we examined mitochondrial membrane potential and the activity of mitochondrial ATP synthesis in the transmitochondrial cybrids, but no significant impairment was detected. The data did not support our hypothesis that these disorders in this family are caused by mtDNA mutation(s).
近期研究表明，线粒体DNA（mtDNA）的突变/多态性与神经精神疾病有关。我们鉴定出一名患有重度抑郁症和癫痫的患者。先证者家系中的一些家庭成员患有双相情感障碍、抑郁症、自杀行为或未另行特指的精神障碍。遗传模式符合低外显率的母系遗传。我们推测该家族中的精神障碍可能与母系遗传的线粒体DNA（mtDNA）突变有关。我们对先证者的整个mtDNA进行了测序。在先证者检测到的34个碱基替换中，两个纯质的、非同义的mtDNA单碱基替换，MT-ND1基因中的T3394C和MT-ATP6基因中的A9115G，被怀疑会导致功能受损，因为前者据报道与疾病相关，而后者非常罕见。为了研究这些替换的功能结果，我们检测了线粒体杂交细胞中的线粒体膜电位和线粒体ATP合成活性，但未检测到明显受损。数据不支持我们的假设，即该家族中的这些疾病是由mtDNA突变引起的。
