[Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) with the A3243G mutation of the tRNALeu(UUR) gene of mtDNA in native American haplogroup B2]. / Encefalomiopatía mitocondrial, acidosis láctica y accidentes cerebrovasculares (MELAS) con la mutación A3243G en el gen ARNtLeu(UUR) del ADNmt en el haplogrupo B2 nativo americano.

INTRODUCTION: Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) is, from the clinical point of view, one of the best studied mitochondrial multisystemic disorders. This disease has mainly been associated to the mitochondrial desoxyribonucleic acid (mtDNA) mutation A3243G located in the tRNALeu(UUR) gene. Although a relation between European haplogroups and the presence of the 3243 mutation has not been described, nothing is known about the presence of this mutation in native American haplogroups. CASE REPORT: A 12 year-old female Mexican patient diagnosed with MELAS is reported. Besides neurological, biochemical and cytological examination, we also analyzed the particular mtDNA mutations related to MELAS and the whole genome was sequenced to determine the mitochondrial haplogroup. The A3243G mutation was detected in the patient and maternal relatives (mother and siblings, all of them asymptomatic). The genotype corresponds to the native American haplogroup B2 and contains two private non-synonymous polymorfisms. CONCLUSION: All the members of the family studied present different percentage of the A3243G mutation, being the patient who presented the highest value. The mtDNA genotype corresponds to the native American haplogroup B2 and the private polymorphisms do not confer any phenotypic modification in MELAS syndrome.

Encefalomiopatía mitocondrial, acidosis láctica y accidentes cerebrovasculares (MELAS) con la mutación A3243G en el gen ARNtLeu(UUR) del ADNmt en el haplogrupo B2 nativo americano / Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (melas) with the a3243g mutation of the trnaleu(uur) gene of mtdna in native american haplogroup b2

Introducción. La encefalomiopatía mitocondrial, acidosis láctica y accidentes cerebrovasculares (MELAS) es uno de los síndromes mitocondriales multisistémicos mejor definidos desde el punto de vista clínico. Esta enfermedad se ha asociado preferentemente con la mutación A3243G del ADN mitocondrial (ADNmt) en el gen ARNtLeu(UUR). Aunque los estudios descritos hasta ahora no han mostrado una participación relevante de los haplogrupos mitocondriales europeos en variables fenotípicas que poseen la mutación A3243G, no hay trabajos parecidos en haplogrupos nativos americanos. Caso clínico. Niña mexicana de 12 años de edad diagnosticada de MELAS a quien, además del seguimiento clínico neurológico y las pruebas bioquímicas y citológicas, se le realizó un estudio genético de su ADNmt, que consistió en el análisis de mutaciones puntuales asociadas a MELAS y una secuenciación posterior del genoma completo para determinar el haplogrupo al que pertenecía. Este estudio detectó la presencia de la mutación puntual A3243G en la paciente y los familiares relacionados por vía materna (madre y seis hermanos, todos asintomáticos). El haplogrupo resultó ser el nativo americano B2 y es portador de dos polimorfismos no sinónimos privados. Conclusión. La mutación A3243G se encuentra en distinto porcentaje de heteroplasmia en los diferentes miembros de la familia; es mayor en la paciente. El genotipo mitocondrial corresponde al haplogrupo nativo americano B2 y las mutaciones privadas no parecen conferir ninguna modificación fenotípica en el síndrome MELAS

Introduction. Mitochondrial encephalopathy, lactic acidosis and cerebrovascular accident syndrome (MELAS) is, from the clinical point of view, one of the best studied mitochondrial multisistemic disorders. This disease has mainly been associated to the mitochondrial DNA (mtDNA) mutation A3243G located in the tRNALeu(UUR) gene. Although a relation between European haplogroups and the presence of the 3243 mutation has not been described, nothing is known about the presence of this mutation in native American haplogroups. Case report. A 12 year-old female Mexican patient diagnosed with MELAS is reported. Besides neurological, biochemical and cytological examination, we also analyzed the particular mtDNA mutations related to MELAS and the whole genome was sequenced to determine the mitochondrial haplogroup. The A3243G mutation was detected in the patient and maternal relatives (mother and sibblings, all of them asymthomatic). The genotype corresponds to the native American haplogroup B2 and contains two private non-synonymous polymorfisms. Conclusion. All the members of the family studied present different percentage of the A3243G mutation, being the patient who presented the highest value. The mtDNA genotype corresponds to the native American haplogroup B2 and the private polymorphisms do not confer any phenotypic modification in MELAS syndrome