Department of Child Neurology, National Center of Neurology and Psychiatry (NCNP), National Center Hospital, Tokyo, Japan.
Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Clin Genet. 2018 May;93(5):1103-1106. doi: 10.1111/cge.13215. Epub 2018 Feb 11.
Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.
线粒体复合物组装因子的遗传异常与脑白质病有关。我们报告了一例 1 岁女孩，在呼吸道感染后出现意识障碍。脑部 MRI 显示脑白质病，双侧黑质、内侧丘脑核和基底核对称性高信号，脑白质和胼胝体有腔隙。脑脊液中的乳酸水平升高，而脑白质和基底核的磁共振波谱显示乳酸峰水平升高，提示线粒体功能障碍。Ⅰ 复合物呼吸酶活性在骨骼肌中降低至 17%至 21%。全外显子组测序发现线粒体复合物 I 组装相关的 NDUFAF3 复合杂合变异(c.342_343insGTG:p.117Valdup，c.505C > A:p.Pro169Thr)。二维、蓝色非变性聚丙烯酰胺凝胶电泳（PAGE）和十二烷基硫酸钠-PAGE 显示 Q 模块（NDUFS2、NDUFS3 和 NDUFA9）和 P 模块（NDUFB10 和 NDUFB11）亚基减少，表明线粒体复合物 I 组装受损。我们的报告扩展了与 NDUFAF3 致病性变异相关的临床表型谱。
