Rötig A, Bessis J L, Romero N, Cormier V, Saudubray J M, Narcy P, Lenoir G, Rustin P, Munnich A
Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U.12, Hôpital des Enfants Malades, Paris, France.
Am J Hum Genet. 1992 Feb;50(2):364-70.
Two sisters in the first year of life presented with a proximal tubulopathy of unknown etiology. They subsequently developed a pluritissular disorder including diabetes mellitus, skin abnormalities, mitochondrial myopathy with ragged-red fibers, and cerebellar ataxia. Their mother had ptosis, ophthalmoplegia, and muscle weakness. Analysis of the mitochondrial respiratory chain showed a complex III deficiency in both skeletal muscle and lymphocytes of the second girl. Southern blot analysis provided evidence for a heteroplasmic partial duplication of the mtDNA (26 kb), involving one full-length and one partly deleted mitochondrial genome and with one single abnormal junction between the genes for ATPase 6 and cytochrome b. Using PCR amplification of lymphocyte DNA, we were able to detect minute amounts of duplicated molecules in the mother, which provided evidence for maternal inheritance of the partial duplication. While maternal transmission of point mutations have been reported in Leber disease, retinitis pigmentosa, and MERRF disease, this observation is, to our knowledge, the first example of a maternally inherited duplication of the mitochondrial genome in man.
两名一岁女童出现病因不明的近端肾小管病。她们随后发展为多系统疾病，包括糖尿病、皮肤异常、伴有破碎红纤维的线粒体肌病和小脑共济失调。她们的母亲有上睑下垂、眼肌麻痹和肌无力。线粒体呼吸链分析显示，第二个女孩的骨骼肌和淋巴细胞中存在复合体III缺陷。Southern印迹分析提供了线粒体DNA（26 kb）异质性部分重复的证据，涉及一个全长和一个部分缺失的线粒体基因组，且在ATPase 6和细胞色素b基因之间有一个单一的异常连接。通过对淋巴细胞DNA进行PCR扩增，我们能够在母亲体内检测到微量的重复分子，这为部分重复的母系遗传提供了证据。虽然在Leber病、色素性视网膜炎和肌阵挛性癫痫伴破碎红纤维病中已报道了点突变的母系传递，但据我们所知，这一观察结果是人类线粒体基因组母系遗传重复的首个实例。
