title: Late-onset ptosis and myopathy in a patient with a heterozygous insertion in POLG2.
abstract: Polymerase gamma 1 (POLG) mutations are a frequent cause of both autosomal dominant and recessive complex neurological phenotypes. In contrast, only a single pathogenic mutation in one patient was reported in POLG2 so far. Here we describe a 62-year-old woman, carrying a novel heterozygous sequence variant in the POLG2 gene. She developed bilateral ptosis at 30 years of age, followed by exercise intolerance, muscle weakness and mild CK increase in her late forties. Muscle histology and respiratory chain activities were normal. Southern blot and long range PCR detected multiple mtDNA deletions, but no depletion in muscle DNA. Sequencing of POLG, PEO1, ANT1, OPA1 and RRM2B showed normal results. A novel heteroallelic 24 bp insertion (c.1207_1208ins24) was detected in POLG2. This 24 bp insertion into exon 7 causes missplicing and loss of exon 7 in myoblast cDNA. We did not detect POLG2 mutations in 62 patients with multiple mtDNA deletions in muscle DNA, suggesting that POLG2 mutations may represent a rare cause of autosomal dominant PEO.
authors.affiliation: Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.forename: Birgit
authors.initials: B
authors.lastname: Czermin
authors.forename: Solvig
authors.initials: S
authors.lastname: Muller-Ziermann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Bulst
authors.forename: Joanna D
authors.initials: JD
authors.lastname: Stewart
authors.forename: Gavin
authors.initials: G
authors.lastname: Hudson
authors.forename: Peter
authors.initials: P
authors.lastname: Schneiderat
authors.forename: Angela
authors.initials: A
authors.lastname: Abicht
authors.forename: Elke
authors.initials: E
authors.lastname: Holinski-Feder
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
mesh_terms: D001483:Base Sequence; D001763:Blepharoptosis / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005858:Germany; D006801:Humans; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D010375:Pedigree
chemical_list: D004259:DNA-Directed DNA Polymerase; C544932:POLG2 protein, human
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