title: Two novel mutations in PEO1 (twinkle) gene associated with chronic external ophthalmoplegia.
abstract: Maintenance and replication of mitochondrial DNA require the concerted action of several factors encoded by nuclear genome. The mitochondrial helicase Twinkle is a key player of replisome machinery. Heterozygous mutations in its coding gene, PEO1, are associated with progressive external ophthalmoplegia (PEO) characterised by ptosis and ophthalmoparesis, with cytochrome c oxidase (COX)-deficient fibres, ragged-red fibres (RRF) and multiple mtDNA deletions in muscle. Here we describe clinical, histological and molecular features of two patients presenting with mitochondrial myopathy associated with PEO. PEO1 sequencing disclosed two novel mutations in exons 1 and 4 of the gene, respectively. Although mutations in PEO1 exon 1 have already been described, this is the first report of mutation occurring in exon 4.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Elisa
authors.initials: E
authors.lastname: Fassone
authors.forename: Andreina
authors.initials: A
authors.lastname: Bordoni
authors.forename: Monica
authors.initials: M
authors.lastname: Sciacco
authors.forename: Valeria
authors.initials: V
authors.lastname: Lucchini
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Mafalda
authors.initials: M
authors.lastname: Rizzuti
authors.forename: Irene
authors.initials: I
authors.lastname: Colombo
authors.forename: Laura
authors.initials: L
authors.lastname: Napoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ciscato
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cosi
authors.forename: Martina
authors.initials: M
authors.lastname: Collotta
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D004265:DNA Helicases / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human