title: Pan-American mDNA haplogroups in Chilean patients with Leber's hereditary optic neuropathy.
abstract: OBJECTIVE
  The clinical impact of mDNA mutations on the development of Leber hereditary optic neuropathy (LHON) may be modulated by mitochondrial haplogroups, which vary across populations. The aim of this research was to determine the clinical spectrum and molecular characteristics, including the haplogroup, of 15 South American families with LHON.
  
  
  METHODS
  This study was a prospective, observational study conducted between March 2006 and August 2012. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular studies were conducted at the Biomedical Sciences Institute (ICBM) of the University of Chile. Fifteen index cases were identified with molecular analysis after initial neuroophthalmic examination at different centers throughout Chile. Clinical features of patients with LHON and maternal relatives of the 15 families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mDNA mutations (m.3460G>A, m.11778G>A, or m.14484T>C) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplogroups were determined with direct sequencing of two hypervariable regions (HV1 and HV2) and compared with reference sequences.
  
  
  RESULTS
  The m.11778G>A mutation was found in 59 subjects (78.7%), the m.14484T>C mutation was found in 12 subjects (16.0%), and the m.3460G>A mutation was found in four (5.3%) subjects. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.7%) were male, and five (19.3%) were female. Twelve families (80%) had Amerindian haplogroups: One family had the A2 haplogroup, four families had the B2i2 haplogroup, six families had the C1b haplogroup, and one family had the D1g haplogroup.
  
  
  CONCLUSIONS
  In this limited sample size, the Amerindian haplogroup A2 was associated with delayed onset of disease in this population. Patients with haplogroup C retained better vision than the patients with other haplogroups in this population. Disease in subjects with haplogroup D appeared to be underrepresented compared to the population at large.
authors.affiliation: Departamento de Oftalmología, Hospital Clínico "José Joaquín Aguirre," Universidad de Chile, Santiago, Chile ; Department of Ophthalmology, University of Washington, Seattle, WA.
authors.forename: Pablo
authors.initials: P
authors.lastname: Romero
authors.affiliation: Departamento de Neuro-oftalmología Instituto Chileno de Neurocirugía, Santiago, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Fernández
authors.affiliation: Department of Ophthalmology, University of Washington, Seattle, WA.
authors.forename: Mark
authors.initials: M
authors.lastname: Slabaugh
authors.affiliation: Departamento de Oftalmología, Hospital Clínico "José Joaquín Aguirre," Universidad de Chile, Santiago, Chile.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Seleme
authors.affiliation: Servicio de Oftalmología, Hospital Regional de Concepción, Santiago, Chile.
authors.forename: Nury
authors.initials: N
authors.lastname: Reyes
authors.affiliation: Departamento de Oftalmología, Hospital Clínico "José Joaquín Aguirre," Universidad de Chile, Santiago, Chile.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gallardo
authors.affiliation: Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Luisa
authors.initials: L
authors.lastname: Herrera
authors.affiliation: Departamento de Oftalmología. Universidad Católica de Chile, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Peña
authors.affiliation: Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Pezo
authors.affiliation: Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Moraga
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002677:Chile; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010641:Phenotype
chemical_list: D004272:DNA, Mitochondrial