Zeviani M, Muntoni F, Savarese N, Serra G, Tiranti V, Carrara F, Mariotti C, DiDonato S
Divisione di Biochimica e Genetica, Istituto Nazionale Neurologico C. Besta, Milano, Italia.
Eur J Hum Genet. 1993;1(1):80-7. doi: 10.1159/000472390.
Several members of a three-generation kindred from Sardinia were affected by a maternally inherited syndrome characterized by features of both myoclonus epilepsy with ragged-red fibers (MERRF) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Clinically, symptoms such as myoclonus epilepsy, neural deafness and ataxia were variably associated with stroke-like episodes and/or migrainous attacks. Morphologically, numerous MELAS-associated SDH-stained vessels were observed in muscle biopsies, either alone or in combination with ragged-red fibers, the morphological hallmark of MERRF. Sequence analysis of the mtDNA tRNA genes revealed the presence of a single, heteroplasmic T-->C transition at nt 8356, in the region of the tRNA(Lys) gene corresponding to the T-psi-C stem. The T-->C(8356) transition was exclusively found in the maternal lineage of our family, and the relative amount of the mutant mtDNA species in muscle was correlated with the severity of the clinical presentation. Therefore, we propose that the T-->C(8356) transition is responsible for the mitochondrial encephalomyopathy found in our family, and must be added to the expanding list of the pathogenetically relevant mutations of human mtDNA.
来自撒丁岛的一个三代家族中的几名成员患有一种母系遗传综合征，其特征兼具肌阵挛性癫痫伴破碎红纤维（MERRF）和线粒体脑肌病伴乳酸酸中毒和卒中样发作（MELAS）。临床上，肌阵挛性癫痫、神经性耳聋和共济失调等症状与卒中样发作和/或偏头痛发作有不同程度的关联。形态学上，在肌肉活检中观察到许多与MELAS相关的琥珀酸脱氢酶（SDH）染色的血管，单独出现或与破碎红纤维同时出现，破碎红纤维是MERRF的形态学标志。线粒体DNA（mtDNA）tRNA基因的序列分析显示，在对应于T-ψ-C茎的tRNA（Lys）基因区域，存在一个单一的异质性T→C转换，位于核苷酸8356处。T→C（8356）转换仅在我们家族的母系中发现，肌肉中突变mtDNA种类的相对数量与临床表现的严重程度相关。因此，我们认为T→C（8356）转换是导致我们家族中线粒体脑肌病的原因，必须添加到人类mtDNA致病相关突变不断增加的列表中。
