Mitochondria

Severe epilepsy as the major symptom of new mutations in the mitochondrial tRNAPhe gene

Severe epilepsy as the major symptom of new mutations in the mitochondrial tRNAPhe gene

Abstract:

Objective:
To present 2 families with maternally inherited severe epilepsy as the main symptom of mitochondrial disease due to point mutations at position 616 in the mitochondrial tRNAPhe (MT-TF) gene.

Methods:
Histologic stainings were performed on skeletal muscle slices from the 2 index patients. Oxidative phosphorylation activity was measured by oxygraphic and spectrophotometric methods. The patients’ complete mitochondrial DNA (mtDNA) and the relevant mtDNA region in maternal relatives were sequenced.

Results:
Muscle histology showed only decreased overall COX staining, while a combined respiratory chain defect, most severely affecting complex IV, was noted in both patients’ skeletal muscle. Sequencing of the mtDNA revealed in both patients a mutation at position 616 in the MT-TF gene (T>C or T>G). These mutations disrupt a base pair in the anticodon stem at a highly conserved position. They were apparently homoplasmic in both patients, and had different heteroplasmy levels in the investigated maternal relatives.

Conclusions:
Deleterious mutations in the mitochondrial tRNAPhe may solely manifest with epilepsy when segregating to homoplasmy. They may be overlooked in the absence of lactate accumulation and typical mosaic mitochondrial defects in muscle.

Citation:

  • Zsurka, G., Hampel, K.G., Nelson, I., Jardel, C., Mirandola, S.R., Sassen, R., Kornblum, C., Marcorelles, P., Lavoué, S., Lombès, A. and Kunz, W.S. (2010). Severe epilepsy as the major symptom of new mutations in the mitochondrial tRNAPhe gene. Neurology, 74(6), 507-512.

Source Link:
http://www.n.neurology.org/content/74/6/507.short

Keywords

Peoples: - | Places: - | Topics: mitochondrial tRNAPhe gene | DNA Type: mtDNA

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

you're currently offline