title: Longitudinal clinical follow-up of a large family with the R357P Twinkle mutation.
abstract: OBJECTIVE
  Autosomal dominant progressive external ophthalmoplegia due to PEO1 mutations is considered relatively benign, but no data about long-term progression of this disease have been reported. The aim of this study was to provide a 16-year clinical follow-up of autosomal dominant progressive external ophthalmoplegia due to the p.R357P gene mutation in PEO1.
  
  
  METHODS
  Twenty-two members of an Irish-American family were examined in 1996, when PEO1 sequencing revealed a c.1071G>C/p.R357P mutation in 9 of them. We reexamined the family in 2012 using a standardized clinical protocol. Autosomal dominant progressive external ophthalmoplegia due to the p.R357P PEO1 mutation is a late-onset ocular myopathy beginning with ptosis and progressing slowly. Ophthalmoparesis, if present, is mild and evident only by neurological examination.
  
  
  CONCLUSIONS
  Our results are important for prognosis and genetic counseling.
authors.affiliation: Unidad de Enfermedades Neuromusculares, Servicio de Neurología, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Seville, Spain2Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Madrid, Spain3Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: Carmen
authors.initials: C
authors.lastname: Paradas
authors.forename: Pilar
authors.initials: P
authors.lastname: Camaño
authors.forename: David
authors.initials: D
authors.lastname: Otaegui
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Oz
authors.forename: Valentina
authors.initials: V
authors.lastname: Emmanuele
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
mesh_terms: D001120:Arginine / Q000235:genetics*; D001763:Blepharoptosis / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000235:genetics*; D011392:Proline / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D001120:Arginine; D011392:Proline; D004265:DNA Helicases; C431576:TWNK protein, human
references.citation: Br J Ophthalmol. 2012 Jun;96(6):841-5
references.pmid: 22493036
references.citation: Neuromuscul Disord. 2009 Dec;19(12):845-8
references.pmid: 19853444
references.citation: Nat Genet. 2001 Jul;28(3):223-31
references.pmid: 11431692
references.citation: Nat Genet. 2007 Jun;39(6):776-80
references.pmid: 17486094
references.citation: Ann Neurol. 2007 Dec;62(6):579-87
references.pmid: 17722119
references.citation: Orbit. 2012 Apr;31(2):114-8
references.pmid: 22489854
references.citation: J Biol Chem. 2012 Apr 27;287(18):14545-56
references.pmid: 22383523
references.citation: Neuromuscul Disord. 2007 Oct;17(9-10):677-80
references.pmid: 17614277
references.citation: J Neurol. 2008 Sep;255(9):1384-91
references.pmid: 18575922
references.citation: Brain. 2009 Jun;132(Pt 6):1553-62
references.pmid: 19304794
references.citation: Science. 2000 Aug 4;289(5480):782-5
references.pmid: 10926541
references.citation: Nat Genet. 2001 Jul;28(3):211-2
references.pmid: 11431686
references.citation: Pharmacoeconomics. 1998 Apr;13(4):421-33
references.pmid: 10178666
references.citation: Neurology. 2010 May 18;74(20):1619-26
references.pmid: 20479361
references.citation: Eur J Neurol. 2011 Mar;18(3):436-41
references.pmid: 20880070