title: Multiplex MALDI-TOF MS detection of mitochondrial variants in Brazilian patients with hereditary optic neuropathy.
abstract: Leber hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral vision loss. More than 95% of LHON cases are associated with one of the three main mtDNA mutations: G11778A, T14484C, and G3460A. The other 5% of cases are due to other rare mutations related to the disease. The aim of this study was to identify the prevalence and spectrum of LHON mtDNA mutations, including the haplogroup, in a cohort of Brazilian patients with optic neuropathy and to evaluate the usefulness of iPLEX Gold/matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) technology in detecting LHON mutations.
  
  
  
  We analyzed a total of 101 patients; 67 had a clinical diagnosis of LHON and 34 had optic neuropathy of unknown etiology. Direct sequencing and iPLEX Gold/MALDI-TOF MS were used to screen for the most common pathogenic point mutations in LHON, together with the rare mutations G3733A, C4171A, T10663C, G14459A, C14482G, A14495G, C14568T, and C14482A.
  
  
  
  We identified mutations in 36 patients, of whom 83.3% carried the G11778A mutation and 16.7% carried the T14484C mutation. In individuals with mutations, the haplogroups found were L1/L2, L3, C, R, U, D, and H. Rare mutations were not detected in any of the patients analyzed.
  
  
  
  The frequencies of the main LHON mutations were similar to those previously reported for Latin America. A different frequency was found only for the A3460G mutation. The most frequent haplogroups identified were of African origin. The iPLEX Gold/MALDI-TOF MS technology proved to be highly accurate and efficient for screening mutations and identifying the haplogroups related to LHON. The MassArray platform, combined with other techniques, enabled definitive diagnosis of LHON in 36% (36/101) of the cases studied.
authors: Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), CP 6010, Av. Cândido Rondon 400, Cidade Universitária Zeferino Vaz, 13083-875, Campinas, SP, Brazil.
authors: Paulo Maurício do Amôr Divino
authors: PM
authors: Miranda
authors: Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), CP 6010, Av. Cândido Rondon 400, Cidade Universitária Zeferino Vaz, 13083-875, Campinas, SP, Brazil.
authors: Sueli
authors: S
authors: Matilde da Silva-Costa
authors: Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), CP 6010, Av. Cândido Rondon 400, Cidade Universitária Zeferino Vaz, 13083-875, Campinas, SP, Brazil.
authors: Juliane Cristina
authors: JC
authors: Balieiro
authors: Department of Ophthalmology and Otorhinolaringology, Faculty of Medical Sciences, University of Campinas (UNICAMP).
authors: Marcela Scabello Amaral
authors: MS
authors: Fernandes
authors: Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), CP 6010, Av. Cândido Rondon 400, Cidade Universitária Zeferino Vaz, 13083-875, Campinas, SP, Brazil.
authors: Rogério Marins
authors: RM
authors: Alves
authors: Department of Medical Genetics, University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo 126, Cidade Universitária Zeferino Vaz, 13083-887, Campinas, SP, Brazil.
authors: Andrea Trevas Maciel
authors: AT
authors: Guerra
authors: Department of Ophthalmology and Otorhinolaringology, Faculty of Medical Sciences, University of Campinas (UNICAMP).
authors: Ana Maria
authors: AM
authors: Marcondes
authors: Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), CP 6010, Av. Cândido Rondon 400, Cidade Universitária Zeferino Vaz, 13083-875, Campinas, SP, Brazil.
authors: Edi Lúcia
authors: EL
authors: Sartorato
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D004272:DNA, Mitochondrial