title: Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia.
abstract: One form of familial progressive external ophthalmoplegia with multiple mitochondrial DNA deletions recently has been associated with mutations in POLG1, the gene encoding pol gammaA, the catalytic subunit of mitochondrial DNA polymerase. We screened the POLG1 gene in several PEO families and identified five different heterozygous missense mutations of POLG1 in 10 autosomal dominant families. Recessive mutations were found in three families. Our data show that mutations of POLG1 are the most frequent cause of familial progressive external ophthalmoplegia associated with accumulation of multiple mitochondrial DNA deletions, accounting for approximately 45% of our family cohort.
authors.affiliation: Unit of Molecular Neurogenetics-Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, National Neurological Institute C. Besta, Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lamantea
authors.forename: Valeria
authors.initials: V
authors.lastname: Tiranti
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.forename: Francesco
authors.initials: F
authors.lastname: Bono
authors.forename: Serena
authors.initials: S
authors.lastname: Servidei
authors.forename: Alex
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: Hans
authors.initials: H
authors.lastname: Spelbrink
authors.forename: Laura
authors.initials: L
authors.lastname: Silvestri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Casari
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000502:physiology*; D009886:Ophthalmoplegia / Q000235:genetics*; D010375:Pedigree
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human