Université Paris Descartes, AP-HP Hôpital Necker-Enfants Malades et Inserm U781 et U797, Départements de Génétique, de Radiologie pédiatrique et des Maladies du développement, Paris, France.
J Med Genet. 2011 Jan;48(1):16-23. doi: 10.1136/jmg.2010.079624. Epub 2010 Oct 23.
To identify a consistent pattern of brain MRI imaging in primary complex I deficiency. Complex I deficiency, a major cause of respiratory chain dysfunction, accounts for various clinical presentations, including Leigh syndrome. Human complex I comprises seven core subunits encoded by mitochondrial DNA (mtDNA) and 38 core subunits encoded by nuclear DNA (nDNA). Moreover, its assembly requires six known and many unknown assembly factors. To date, no correlation between genotypes and brain MRI phenotypes has been found in complex I deficiencies.
The brain MRIs of 30 patients carrying known mutation(s) in genes involved in complex I were retrospectively collected and compared with the brain MRIs of 11 patients carrying known mutations in genes involved in the pyruvate dehydrogenase (PDH) complex as well as 10 patients with MT-TL1 mutations.
All complex I deficient patients showed bilateral brainstem lesions (30/30) and 77% (23/30) showed anomalies of the putamen. Supratentorial stroke-like lesions were only observed in complex I deficient patients carrying mtDNA mutations (8/19) and necrotising leucoencephalopathy in patients with nDNA mutations (4/5). Conversely, the isolated stroke-like images observed in patients with MT-TL1 mutations, or the corpus callosum malformations observed in PDH deficient patients, were never observed in complex I deficient patients.
A common pattern of brain MRI imaging was identified with abnormal signal intensities in brainstem and subtentorial nuclei with lactate peak as a clue of complex I deficiency. Combining clinico-biochemical data with brain imaging may therefore help orient genetic studies in complex I deficiency.
确定原发性复合物 I 缺陷的脑 MRI 成像的一致模式。复合物 I 缺陷是呼吸链功能障碍的主要原因，其临床表现包括 Leigh 综合征。人类复合物 I 由线粒体 DNA（mtDNA）编码的七个核心亚基和核 DNA（nDNA）编码的 38 个核心亚基组成。此外，其组装需要六个已知和许多未知的组装因子。迄今为止，复合物 I 缺陷中尚未发现基因型与脑 MRI 表型之间的相关性。
回顾性收集了 30 名携带已知突变的复合物 I 相关基因的患者的脑部 MRI，并与 11 名携带丙酮酸脱氢酶（PDH）复合物相关基因已知突变的患者和 10 名 MT-TL1 突变患者的脑部 MRI 进行了比较。
所有复合物 I 缺陷患者均表现为双侧脑干病变（30/30），77%（23/30）表现为壳核异常。仅在携带 mtDNA 突变的复合物 I 缺陷患者中观察到幕上卒中样病变（8/19），在 nDNA 突变患者中观察到坏死性白质脑病（4/5）。相反，在 MT-TL1 突变患者中观察到的孤立性卒中样图像，或在 PDH 缺陷患者中观察到的胼胝体畸形，从未在复合物 I 缺陷患者中观察到。
确定了脑 MRI 成像的共同模式，表现为脑干和桥脑下核的异常信号强度，以乳酸性峰为复合物 I 缺陷的线索。因此，将临床生化数据与脑成像相结合，可能有助于指导复合物 I 缺陷的基因研究。
