Additive effects of POLG1 and ANT1 mutations in a complex encephalomyopathy.
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.
Galassi
Giuliana
G
Department of Neuroscience, University of Modena, Modena, Italy.
Lamantea
Eleonora
E
Invernizzi
Federica
F
Tavani
Federica
F
Pisano
Isabella
I
Ferrero
Ileana
I
Palmieri
Luigi
L
Zeviani
Massimo
M
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
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