title: Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA.
abstract: We studied nine infant patients with a combination of progressive neurological and hepatic failure. Eight children, including two sibling pairs and four singletons, were affected by Alpers' hepatopathic poliodystrophy. A ninth baby patient suffered of a severe floppy infant syndrome associated with liver failure. Analysis of POLG1, the gene encoding the catalytic subunit of mitochondrial DNA polymerase, revealed that all the patients carried different allelic mutations in this gene. POLG1 is a major disease gene in mitochondrial disorders. Mutations in this gene can be associated with multiple deletions, depletion or point mutations of mitochondrial DNA (mtDNA). In turn, these different molecular phenotypes dictate an extremely heterogeneous spectrum of clinical outcomes, ranging from adult-onset progressive ophthalmoplegia to juvenile ataxic syndromes with epilepsy, to rapidly fatal hepatocerebral presentations, including Alpers' syndrome.
authors.affiliation: Unit of Molecular Neurogenetics, Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, National Institute of Neurology, Milano, Italy.
authors.forename: Gianfrancesco
authors.initials: G
authors.lastname: Ferrari
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.forename: Alice
authors.initials: A
authors.lastname: Donati
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.forename: Egill
authors.initials: E
authors.lastname: Briem
authors.forename: Franco
authors.initials: F
authors.lastname: Carrara
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: René
authors.initials: R
authors.lastname: Santer
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D001921:Brain / Q000473:pathology; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D017093:Liver Failure / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human