title: Progressive external ophthalmoplegia in southwestern Finland: a clinical and genetic study.
abstract: BACKGROUND
  Progressive external ophthalmoplegia (PEO) is a common phenotype of mitochondrial disease. Molecular etiologies include sporadic, large-scale deletions in mitochondrial DNA (mtDNA), multiple mtDNA deletions secondary to autosomal dominant or recessive mutations and mtDNA point mutations.
  
  
  METHODS
  We studied the prevalence and clinical and genetic characteristics of PEO in a defined population in southwestern Finland. A total of 620 patients were first identified from the patient registry at the Turku University Hospital over an 18-year period. The medical records of these patients were scrutinized, and those with clinical features compatible with PEO were ascertained.
  
  
  RESULTS
  We identified 10 patients with possible PEO. The patients were examined clinically, and DNA was analyzed for mtDNA deletions and for the m.3243A>G and m.8344A>G mtDNA point mutations. The ANT1, PEO1, POLG1 and POLG2 genes were sequenced. We confirmed the clinical diagnosis of PEO in 6 patients. Large-scale mtDNA deletions were detected in 3 out of 6 PEO patients and mutations in the POLG1 gene in 1 out of 6. We did not find any mutations in the ANT1, PEO1 or POLG2 genes.
  
  
  CONCLUSIONS
  Our results suggest that molecular investigation of patients with PEO, either sporadic or familial, should start with an analysis for mtDNA deletions, followed by an analysis of the POLG1 gene.
authors.affiliation: Department of Neurology, Turku University Hospital, Turku, Finland.
authors.forename: Mika H
authors.initials: MH
authors.lastname: Martikainen
authors.forename: Reetta
authors.initials: R
authors.lastname: Hinttala
authors.forename: Matias
authors.initials: M
authors.lastname: Röyttä
authors.forename: Satu
authors.initials: S
authors.lastname: Jääskeläinen
authors.forename: Maria
authors.initials: M
authors.lastname: Wendelin-Saarenhovi
authors.forename: Riitta
authors.initials: R
authors.lastname: Parkkola
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
mesh_terms: D033741:Adenine Nucleotide Translocator 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004265:DNA Helicases / Q000235:genetics; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D017246:Ophthalmoplegia, Chronic Progressive External / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D017354:Point Mutation; D015995:Prevalence; D017384:Sequence Deletion
chemical_list: D033741:Adenine Nucleotide Translocator 1; D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; C544932:POLG2 protein, human; D004265:DNA Helicases; C431576:TWNK protein, human