title: Additive effects of POLG1 and ANT1 mutations in a complex encephalomyopathy.
abstract: MtDNA instability is associated with a wide spectrum of clinical presentations, from dominant or recessive progressive external ophthalmoplegia (PEO) to juvenile-onset spino-cerebellar ataxia and epilepsy (SCAE) or infantile Alpers-Huttenlocher syndrome. We present here the clinical and molecular features of a patient with a clinical presentation characterized initially by PEO with mtDNA multiple deletions lately evolving into a severe neurological syndrome, which included sensory and cerebellar ataxia, peripheral neuropathy, parkinsonism, and depression. This complex phenotype is the result of mutations in two distinct proteins, ANT1 and PolgammaA, which cause additive, deleterious effects on mtDNA maintenance and integrity.
authors.affiliation: Department of Neuroscience, University of Modena, Modena, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Galassi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.forename: Federica
authors.initials: F
authors.lastname: Invernizzi
authors.forename: Federica
authors.initials: F
authors.lastname: Tavani
authors.forename: Isabella
authors.initials: I
authors.lastname: Pisano
authors.forename: Ileana
authors.initials: I
authors.lastname: Ferrero
authors.forename: Luigi
authors.initials: L
authors.lastname: Palmieri
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000145:classification / Q000235:genetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008715:Methionine / Q000235:genetics; D017237:Mitochondrial Encephalomyopathies / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D013997:Time Factors; D014633:Valine / Q000235:genetics
chemical_list: D033741:Adenine Nucleotide Translocator 1; D000255:Adenosine Triphosphate; D008715:Methionine; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D014633:Valine