Clinical and biochemical characteristics in patients with a high mutant load of the mitochondrial T8993G/C mutations
Clinical and biochemical characteristics in patients with a high mutant load of the mitochondrial T8993G/C mutations
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DOI：
10.1002/ajmg.a.31194
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发表时间：
2006-04-15
影响因子：
2
通讯作者：
Smeitink, J
中科院分区：
文献类型：
--
作者：
Morava, E;Rodenburg, RJ;Smeitink, J
我们回顾性分析了11名儿童的临床、组织学和生化数据，其中5名携带母系遗传的线粒体T8993 C，6名携带ATP合成酶6基因的T8993 G点突变。在肌肉和血液中的异质性百分比为95%或更高。所有患者均有早期临床表现，包括肌肉张力减退、严重锥体外系功能障碍和头颅MRI证实的Leigh病。在肌肉和血液中携带T8993 C突变的高突变负荷患者中，观察到临床进展较慢，感觉神经元受累更频繁。未发现组织学异常，11例中有9例检测到ATP产生减少，所有儿童均缺乏复合物V活性。呼吸酶复合物II和IV的活动是正常的，而相关的复合物I和III的缺陷，在两名患者。同一基因不同突变的两组患者的生化指标无明显差异。复合物V酶缺乏的程度和表型的严重程度之间没有相关性。我们证实了我们的患者中复合物V的组装/稳定性受损。这是第一次报告的活动减少和受损的装配/稳定性的复合物V的T8993 C突变患者在肌肉组织中测量。(c)2006 Wiley-Liss，Inc.
We retrospectively analyzed the clinical, histological, and biochemical data of 11 children, five of which carried the maternally-inherited mitochondrial T8993C and six carrying the T8993G point mutations in the ATP synthase 6 gene. The percentage of heteroplasmy was 95% or higher in muscle and in blood. All patients had an early clinical presentation with muscle hypotonia, severe extrapyramidal dysfunction and Leigh disease demonstrated by the cranial MRI. A slower clinical progression and more frequent sensory-neuronal involvement were noted in the patients carrying the T8993C mutation in a high Mutation load in muscle and blood. No histological abnormality was found, In 9 out of 11 patients a decreased ATP production was detected, and complex V activity was deficient in all children. The activities of the respiratory enzyme complexes II and IV were normal, whereas an associated combined complex I and III deficiency were present in two patients. No obvious difference was found between the biochemical parameters of the two patient groups harboring different mutations in the same gene. No correlation was found between the degree of complex V enzyme deficiency and the severity of the phenotype. We confirmed an impaired assembly/stability of complex V in our patients. This is the first report of decreased activity and impaired assembly/stability of complex V in patients with T8993C mutations measured in muscle tissue. (c) 2006 Wiley-Liss, Inc.