Pan-American mDNA haplogroups in Chilean patients with Leber's hereditary optic neuropathy.

PURPOSE: 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.

Neuritis óptica: protocolo latinoamericano / Optic neuritis: latinamerican protocol

Para definir las características de la neuritis óptica (NO) en países del hemisferio sur, se efectuó un estudio prospectivo en 4 ciudades entre los paralelos 32 y 37 de latitud sur en Argentina y Chile. Se estudiaron 85 pacientes de los que se consignó edad, sexo, compromiso monocular o binocular y presencia de dolor ocular. Se examinó la agudeza visual, reflejos pupilares, motilidad ocular, fondo de ojo y campo visual con perímetro de cúpula. Se esperó una recuperación de la visión de colores y potencial visual evocado. Todos los pacientes fueron examinados por un solo neurólogo en cada centro de referencia. El promedio de edad de nuestros pacientes fue de 33 años (con un rango de 2,5 a 59 años). 71 por ciento eran mujeres y 29 por ciento hombres. En el 74 por ciento de los casos NO fue unilateral y en el 26 por ciento bilateral. Los pacientes relataron en forma espontánea una historia de dolor y retrobulbar en el 41 por ciento. 74 por ciento de nuestros casos presentaron, como alteración del campo visual, un escotoma central. Las características clínicas de los pacientes de este estudio son semejantes a las publicadas en la literatura del hemisferio norte; excepto en la mayor frecuencia de neuritis bulbar en nuestros casos