title: Expanding the clinical phenotypes of MT-ATP6 mutations.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ester
authors.initials: E
authors.lastname: López-Gallardo
authors.affiliation: 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.
authors.forename: Sonia
authors.initials: S
authors.lastname: Emperador
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain.
authors.forename: Abelardo
authors.initials: A
authors.lastname: Solano
authors.affiliation: 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Llobet
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martín-Navarro
authors.affiliation: 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.
authors.forename: Manuel José
authors.initials: MJ
authors.lastname: López-Pérez
authors.affiliation: Servicio de Bioquímica y Genética Molecular, Hospital Clínico, IDIBAPS, 08036-Barcelona, Spain, Centro de Investigaciones Biomédicas en red de Enfermedades Raras (CIBERER), Spain.
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.affiliation: Servicio de Neurología and Centro de Investigaciones Biomédicas en red de Enfermedades Raras (CIBERER), Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Pineda
authors.affiliation: Departamento de Bioquímica Clínica, Hospital San Joan de Deu, 08950 Barcelona, Spain, Centro de Investigaciones Biomédicas en red de Enfermedades Raras (CIBERER), Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch
authors.affiliation: Clínica Barraquer, 08021 Barcelona, Spain and.
authors.forename: Elena
authors.initials: E
authors.lastname: Barraquer
authors.affiliation: Servicio de Neurología, Complejo Universitario de Navarra, 31008-Pamplona, Spain.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Jericó
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain, Fundación ARAID, Universidad de Zaragoza, 50013 Zaragoza, Spain, Centro de Investigaciones Biomédicas en red de Enfermedades Raras (CIBERER), Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
authors.affiliation: 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, jmontoya@unizar.es.
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007888:Leigh Disease / Q000235:genetics; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D025261:Mitochondrial Proton-Translocating ATPases