title: Point mutations associated with Leber hereditary optic neuropathy in a Latvian population.
abstract: OBJECTIVE
  To study mutations associated with Leber hereditary optic neuropathy (LHON) in patients suspected of having this mitochondrial disorder in a Latvian population. Additional aims were to determine the heteroplasmy status of all non-synonymous polymorphisms identified in the current study and to identify the mitochondrial haplogroups of the studied participants because these factors may contribute to the manifestation of LHON.
  
  
  METHODS
  Twelve patients, including patients in two families, were enrolled in the current study. LHON was suspected based on the findings of ophthalmologic examinations. In clinically affected individuals, the presence of all previously reported LHON-associated mutations was assessed with sequencing analysis. Additionally, the SURVEYOR endonuclease assay was used to detect heteroplasmy. The mitochondrial haplogroups were identified with restriction analysis and the sequencing of hypervariable segment 1.
  
  
  RESULTS
  In one family (mother and son), there was one primary LHON-associated mutation, G11778A. In addition, one rare previously reported LHON-associated polymorphism, A13637G, was detected in two unrelated patients. A non-synonymous polymorphism at T6253C was found in one individual. This mutation was reported in the background of the 3460 mutation among LHON patients in a Chinese population. No non-synonymous point mutations in mitochondrial DNA were found in five of the study participants.
  
  
  CONCLUSIONS
  Molecular analysis of 12 patients with suspected LHON confirmed the diagnosis in four patients and allowed the use of appropriate prophylactic measures and treatment. Further investigations and additional studies of different populations are necessary to confirm the role of the non-synonymous polymorphisms A13637G and T6253C in the manifestation of LHON and the associations of these polymorphisms with mitochondrial haplogroups and heteroplasmy.
authors: Riga Stradins University, Riga, Latvia ; Latvian Biomedical Research and Study Centre, Riga, Latvia.
authors: Aleksandra
authors: A
authors: Aitullina
authors: Kristine
authors: K
authors: Baumane
authors: Solveiga
authors: S
authors: Zalite
authors: Renate
authors: R
authors: Ranka
authors: Egija
authors: E
authors: Zole
authors: Ilva
authors: I
authors: Pole
authors: Svetlana
authors: S
authors: Sepetiene
authors: Guna
authors: G
authors: Laganovska
authors: Viesturs
authors: V
authors: Baumanis
authors: Liana
authors: L
authors: Pliss
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007844:Latvia; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D044465:White People
chemical_list: D004272:DNA, Mitochondrial