Ortigoza-Escobar Juan Darío, Oyarzabal Alfonso, Montero Raquel, Artuch Rafael, Jou Cristina, Jiménez Cecilia, Gort Laura, Briones Paz, Muchart Jordi, López-Gallardo Ester, Emperador Sonia, Pesini Eduardo Ruiz, Montoya Julio, Pérez Belén, Rodríguez-Pombo Pilar, Pérez-Dueñas Belén
Division of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Spain; Division of Child Neurology, Fundación Hospital Asilo de Granollers, Barcelona, Spain.
Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Centro de Biología Molecular Severo Ochoa CSIC-UAM, Departamento de Biología Molecular, Universidad Autónoma de Madrid, IDIPAZ, Spain.
Mitochondrion. 2016 May;28:73-8. doi: 10.1016/j.mito.2016.04.001. Epub 2016 Apr 11.
The genetic causes of Leigh syndrome are heterogeneous, with a poor correlation between the phenotype and genotype. Here, we present a patient with an NDUFS4 mutation to expand the clinical and biochemical spectrum of the disease. A combined defect in the CoQ, PDH and RCC activities in our patient was due to an inappropriate assembly of the RCC complex I (CI), which was confirmed using Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) analysis. Targeted exome sequencing analysis allowed for the genetic diagnosis of this patient. We reviewed 198 patients with 24 different genetic defects causing RCC I deficiency and compared them to 22 NDUFS4 patients. We concluded that NDUFS4-related Leigh syndrome is invariably linked to an early onset severe phenotype that results in early death. Some data, including the clinical phenotype, neuroimaging and biochemical findings, can guide the genetic study in patients with RCC I deficiency.
Leigh综合征的遗传病因具有异质性，其表型与基因型之间的相关性较差。在此，我们报告一名患有NDUFS4突变的患者，以扩展该疾病的临床和生化谱。我们患者中辅酶Q、丙酮酸脱氢酶（PDH）和呼吸链复合体（RCC）活性的联合缺陷是由于RCC复合体I（CI）组装不当所致，这通过蓝色非变性聚丙烯酰胺凝胶电泳（BN-PAGE）分析得以证实。靶向外显子组测序分析实现了该患者的基因诊断。我们回顾了198例由24种不同基因缺陷导致RCC I缺乏的患者，并将他们与22例NDUFS4患者进行了比较。我们得出结论，与NDUFS4相关的Leigh综合征总是与早期发病的严重表型相关，导致早期死亡。一些数据，包括临床表型、神经影像学和生化结果，可为RCC I缺乏患者的基因研究提供指导。
