Analysis of mtDNA A3243G mutation frequency in Hungary

Abstract

<jats:title>Abstract</jats:title><jats:p>The A3243G mutation in the mitochondrial tRNALeu (UUR) gene is one of the most common causes of mitochondrial DNA related disorders. Originally it was described in MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic acidosis, Stroke-like episodes), later it had been found to be associated with various phenotypes. In our study the mutation frequency of the A3243G mtDNA mutation was investigated in patients with maternal sensoneural hearing loss, stroke-like episodes, ataxia and myopathy with undetermined etiology. We screened 631 Hungarian patients in North-East, South-West and Central Hungary between 1999 and 2008 for this mutation. The mtDNA analysis was performed from blood and/or muscle tissue. The A3243G substitution was present in 6 patients in heteroplasmic form. The segregation analysis detected 8 further cases. The frequency of the A3243G mutation was 2.22% in the investigated patients. The A3243G mutation frequency in Hungary does not differ significantly from other countries using similar patient selection criteria, however in Finland a higher mutation rate was found. In studies investigated the mutation frequency of this mutation in diabetes mellitus similarly wide variety was detected as well. We conclude that the study design has a huge impact on the result of the genetic epidemiological investigation analyzing the mutation frequency of the A3243G mutation due to the broad clinical phenotype and the different mutation load in different tissues.</jats:p>

Development of Real-time PCR Kit for Detection and Quantitation of Six Common Mutations A3243G, G3380A, A8344G, T8993G, T8993C, G11778A of Human Mitochondrial Genome

“…Tỷ lệ đột biến này khá gần với tỷ lệ 5,7% mà Truong và các cộng sự [26] trước đây đã phát hiện khi điều tra trên 106 bệnh nhân người Việt Nam nghi bị bệnh ty thể. Trong một nghiên cứu trước đây ở 631 bệnh nhân người Hungary có triệu chứng bệnh ty thể, Gal và các cộng sự [27] đã cho thấy có 2,2% bệnh nhân mang đột biến A3243G. Tỷ lệ này là 1,74% trong một nghiên cứu khác, ở 230 bệnh nhân người Nhật bị giảm khả năng nghe [28].…”

Comportamiento de la mutación mtDNA A3243G en dos familias antioqueñas de pacientes diagnosticados con el síndrome MELAS

“…21 Fue la primera citopatía asociada con una mutación puntual en mtDNA, consecuente con una transición de Adenina → Guanina (A→G) en la posición 3243, en la región que codifica para el tRNALeu; 19,27 esta transición es responsable del 80% de los casos de MELAS 5,7,19 y presenta una gran heterogeneidad genética. [30][31][32] El tRNA Leu está codificado entre los nucleótidos 3230 y 3304, y contiene el factor de terminación de la transcripción mitocondrial (mTERF-, por sus siglas del inglés: Mitochondrial transcription termination factor-[nt3229-nt3256]), necesario para la terminación del transcrito ribosomal 16S; es flanqueado por los genes que codifican para el rRNA 16S (1671-3229) y el gen de la NADH deshidrogenasa I33 (3307-4262) 24 . Todas las mutaciones asociadas con síndrome MELAS son heteroplásmicas, con más del 80% del mtDNA mutado en músculo; la expresión, dependiente de las proporciones de genoma mutante en músculo y cerebro, se hace manifiesta cuando este porcentaje excede el 60%.…”

“…43 La disminución en la tasa de síntesis de proteína (entre 20 -40%) como efecto de la reducción en el número de ribosomas es otro mecanismo que se ha dilucidado. 44 Se han realizado numerosos trabajos en los que se observa asociación de esta mutación con otros trastornos diferentes del síndrome MELAS, como sordera 45,46 diabetes mellitus tipo 2 31,46,47,48 y migraña. 49,50 Esta variabilidad en la presentación clínica de la mutación puede ser debida a la cantidad de heteroplasmia o al contexto genético nuclear.…”