NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy
NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy
复制标题
破坏线粒体复合物 I 组装的 NDUFAF3 变异可能与空洞性白质脑病有关
DOI：
10.1111/cge.13215
复制
发表时间：
2018
影响因子：
3.5
通讯作者：
Nishino I.
中科院分区：
文献类型：
--
作者：
Ishiyama A.;Muramatsu K.;Uchino S.;Sakai C.;Matsushima Y.;Makioka N.;Ogata T.;Suzuki E.;Komaki H.;Sasaki M.;Mimaki M.;Goto Y.-I.;Nishino I.
线粒体复杂组装因子的遗传异常与白质脑病有关。我们报告一位1岁女童在呼吸道感染后出现意识障碍。脑MRI示双侧对称性高强度脑白质病，黑质、内侧丘脑核和基底核，脑白质和胼胝体可见空腔。脊髓液乳酸水平高，脑白质和基底核磁共振显示乳酸水平峰值高，提示线粒体功能障碍。骨骼肌中复合体I的呼吸酶活性降低到17% ~ 21%。全外显子组测序鉴定出化合物杂合变异indufaf3，参与线粒体复合体I的组装(c.342_343insGTG:p。[17] [c] [c] [c] [b] [c]。二维，蓝色原生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，表明线粒体复合体I组装中断。我们的报告扩展了与ndufaf3致病变异相关的临床表型谱。
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 inNDUFAF3, 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 ofNDUFAF3.