Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases.
Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases.
复制标题
DOI：
10.1007/s10545-012-9492-z
复制
发表时间：
2012-09
影响因子：
4.2
通讯作者：
Smeitink, J. A. M.
中科院分区：
文献类型：
--
作者：
Koene, S.;Rodenburg, R. J.;van der Knaap, M. S.;Willemsen, M. A. A. P.;Sperl, W.;Laugel, V.;Ostergaard, E.;Tarnopolsky, M.;Martin, M. A.;Nesbitt, V.;Fletcher, J.;Edvardson, S.;Procaccio, V.;Slama, A.;van den Heuvel, L. P. W. J.;Smeitink, J. A. M.
线粒体复合物I是氧化磷酸化系统中最大的多蛋白酶复合物。该复合物的七个亚基由线粒体编码，其余由核基因组编码。我们回顾了130例（4例新病例和126例文献）编码结构复合物I蛋白或参与其组装的核基因突变的自然病程和体征和症状。由核基因缺陷引起的复合物I缺乏症通常是一种非畸形综合征，其特征是严重的多系统器官受累和预后不良。发病时的年龄可能有所不同，但通常在出生后一年内。最常见的症状包括张力减退、眼球震颤、呼吸异常、锥体束征、肌张力障碍、精神发育迟滞或退化、发育不良和进食问题。特征性症状包括脑干受累、视神经萎缩和MRI显示的Leigh综合征，可合并或不合并内脏受累和乳酸血症。几乎所有的儿童最终都会发展为利氏综合征或白质脑病。25%的患者在6个月内死亡，超过一半的患者在2岁之前死亡，75%的患者在10岁之前死亡。有些病人表现出某些技能的恢复，或者在三十多岁时仍然活着。没有发现任何临床、生化或遗传参数表明生存期延长，也没有观察到明显的基因型-表型相关性，但某些基因的缺陷似乎与预后的好坏、心肌病、Leigh综合征或脑干病变有关。本文的在线版本（doi：10.1007/s10545-012-9492-z）包含补充材料，可供授权用户使用。
Mitochondrial complex I is the largest multi-protein enzyme complex of the oxidative phosphorylation system. Seven subunits of this complex are encoded by the mitochondrial and the remainder by the nuclear genome. We review the natural disease course and signs and symptoms of 130 patients (four new cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis. Age at presentation may vary, but is generally within the first year of life. The most prevalent symptoms include hypotonia, nystagmus, respiratory abnormalities, pyramidal signs, dystonia, psychomotor retardation or regression, failure to thrive, and feeding problems. Characteristic symptoms include brainstem involvement, optic atrophy and Leigh syndrome on MRI, either or not in combination with internal organ involvement and lactic acidemia. Virtually all children ultimately develop Leigh syndrome or leukoencephalopathy. Twenty-five percent of the patients died before the age of six months, more than half before the age of two and 75 % before the age of ten years. Some patients showed recovery of certain skills or are still alive in their thirties . No clinical, biochemical, or genetic parameters indicating longer survival were found. No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions. The online version of this article (doi:10.1007/s10545-012-9492-z) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
11.4
作者：
Dunning, C. J. R.;McKenzie, M.;Ryan, M. T.
通讯作者：
Ryan, M. T.
影响因子：
9.8
作者：
Hoefs, Saskia J. G.;Dieteren, Cindy E. J.;van den Heuvel, Lambert P.
通讯作者：
van den Heuvel, Lambert P.
影响因子：
4.2
作者：
Budde, SMS;van den Heuvel, LPWJ;Smeitink, JAM
通讯作者：
Smeitink, JAM
影响因子：
3.9
作者：
Bénit, P;Beugnot, R;Munnich, A
通讯作者：
Munnich, A
影响因子：
3.8
作者：
Barghuti, Flora;Elian, Khaled;Elpeleg, Orly
通讯作者：
Elpeleg, Orly