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Pablo Romero, Mark Slabaugh, Verónica Fernández, Nicolás Seleme, Patricio Pezo, Luisa Herrera, Mauricio Moraga; Pan-American MtDNA haplogroups in LHON patients. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1357.
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The aim of this research was to determine the clinical spectrum and molecular characterization of fifteen South American families with Leber’s Hereditary Optic Neuropathy (LHON)
This study was conducted between March 2006 and August 2012. Fifteen index cases were identified during neuro-ophthalmic examination at different centers throughout Chile. All patients were referred to the Clinical Hospital of the University of Chile, where the clinical study was conducted. Molecular study was conducted at ICBM (University of Chile). Clinical features of LHON patients and maternal relatives of fifteen families (75 individuals: 26 affected and 49 healthy carriers) were evaluated. The primary mtDNA mutations (G3460A/ND1, G11778A/ND4, or T14484C/ND6) were determined with restriction fragment length polymorphism analysis in all individuals. Mitochondrial haplotypes were determined by direct sequencing of the regions HV1 and HV2 and compared with the reference sequence
The G11778A/ND4 mutation was found in 59 subjects (78.7%), the T14484C/ND6 was found in 12 (16.0%) and the G3460A/ND1 mutation was found in 4 (5.3%) individuals. The average age of onset of symptoms in affected subjects was 22.2 years old (range 3 to 53 years); 21 (80.8%) were male and 5 (19.2%) were female. Average time from symptom onset to presentation was 7.2 days (range 12 hours to 21 days). Time to involvement of the second eye was 53.3 days on average. Twelve families had Amerindian haplogroups: 1 family had A2 haplotype, 4 families had B2i2 haplotype, 6 families had C1b haplotype and 1 family had D1g haplotype. One family had J2b haplotype, associated with European populations, and two families had L1b haplotype, associated with African populations. In five patients the disease onset was after 40 years of age. Subjects with A haplotype on average had a later onset of disease (p=0.001, ANOVA) than those with other haplotypes (47.3 years on average) and subjects with haplotype C were more likely to retain 20/200 or better vision in the better eye than those with other haplotypes (p=0.009, ANOVA)
LHON mutations are necessary but not sufficient for phenotypic expression of disease in patients with LHON mutations and Amerindian haplotypes."A" haplotype may be associated with a delayed onset of disease in this population. Patients with haplotype C retained better vision than patients with other haplotypes in this population
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