López-Gallardo Ester, Emperador Sonia, Solano Abelardo, Llobet Laura, Martín-Navarro Antonio, López-Pérez Manuel José, Briones Paz, Pineda Mercedes, Artuch Rafael, Barraquer Elena, Jericó Ivonne, Ruiz-Pesini Eduardo, Montoya Julio
Departamento de Bioquímica, Biología Molecular y Celular, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain, Centro de Investigaciones Biomédicas en red de Enfermedades Raras (CIBERER), Spain.
Departamento de Bioquímica, Biología Molecular y Celular, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain.
Hum Mol Genet. 2014 Dec 1;23(23):6191-200. doi: 10.1093/hmg/ddu339. Epub 2014 Jun 30.
Mitochondrial DNA mutations at MT-ATP6 gene are relatively common in individuals suffering from striatal necrosis syndromes. These patients usually do not show apparent histochemical and/or biochemical signs of oxidative phosphorylation dysfunction. Because of this, MT-ATP6 is not typically analyzed in many other mitochondrial disorders that have not been previously associated to mutations in this gene. To correct this bias, we have performed a screening of the MT-ATP6 gene in a large collection of patients suspected of suffering different mitochondrial DNA (mtDNA) disorders. In three cases, biochemical, molecular-genetics and other analyses in patient tissues and cybrids were also carried out. We found three new pathologic mutations. Two of them in patients showing phenotypes that have not been commonly associated to mutations in the MT-ATP6 gene. These results remark the importance of sequencing the MT-ATP6 gene in patients with striatal necrosis syndromes, but also within other mitochondrial pathologies. This gene should be sequenced at least in all those patients suspected of suffering an mtDNA disorder disclosing normal results for histochemical and biochemical analyses of respiratory chain.
MT-ATP6基因的线粒体DNA突变在患有纹状体坏死综合征的个体中相对常见。这些患者通常不会表现出明显的氧化磷酸化功能障碍的组织化学和/或生化迹象。因此，在许多先前未与该基因突变相关的其他线粒体疾病中，通常不会对MT-ATP6进行分析。为了纠正这种偏差，我们对大量疑似患有不同线粒体DNA（mtDNA）疾病的患者进行了MT-ATP6基因筛查。在三个病例中，还对患者组织和胞质杂种进行了生化、分子遗传学和其他分析。我们发现了三个新的病理性突变。其中两个在表现出与MT-ATP6基因突变通常无关的表型的患者中。这些结果表明，在患有纹状体坏死综合征的患者中，以及在其他线粒体疾病中，对MT-ATP6基因进行测序具有重要意义。至少在所有怀疑患有mtDNA疾病且呼吸链组织化学和生化分析结果正常的患者中，都应该对该基因进行测序。
