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01-05-2009 | Original Communication

Heteroplasmic mutation in the anticodon-stem of mitochondrial tRNA^Val causing MNGIE-like gastrointestinal dysmotility and cachexia

Authors: Rita Horváth, Andreas Bender, Angela Abicht, Elke Holinski-Feder, Birgit Czermin, Tobias Trips, Peter Schneiderat, Hanns Lochmüller, Thomas Klopstock

Published in: Journal of Neurology | Issue 5/2009

Abstract

While mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is typically associated with mutations in the nuclear gene encoding for thymidine phosphorylase (ECGF1, TYMP), a similar clinical phenotype was described in patients carrying mutations in the nuclear-encoded polymerase gamma (POLG1) as well as a few mitochondrial tRNA genes. Here we report a novel mutation in the mitochondrial tRNA^Val (MTTV) gene in a girl presenting with clinical symptoms of MNGIE-like gastrointestinal dysmotility and cachexia. Clinical, histological, biochemical and single cell investigations were performed. The heteroplasmic m.1630A>G mutation was detected in the mitochondrial tRNA^Val (MTTV) gene in the patient’s muscle, blood leukocytes and myoblasts, as well as in blood DNA of the unaffected mother. We provide clinical, biochemical, histological, and molecular genetic evidence on the single cell level for the pathogenicity of this mutation. Our finding adds to the genetic heterogeneity of MNGIE-like gastrointestinal symptoms and highlights the importance of a thorough genetic workup in case of suspected mitochondrial disease.

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Title: Heteroplasmic mutation in the anticodon-stem of mitochondrial tRNAVal causing MNGIE-like gastrointestinal dysmotility and cachexia
Authors: Rita Horváth
Andreas Bender
Angela Abicht
Elke Holinski-Feder
Birgit Czermin
Tobias Trips
Peter Schneiderat
Hanns Lochmüller
Thomas Klopstock
Publication date: 01-05-2009
Publisher: D. Steinkopff-Verlag
Published in: Journal of Neurology / Issue 5/2009
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-009-5023-8

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Heteroplasmic mutation in the anticodon-stem of mitochondrial tRNA^Val causing MNGIE-like gastrointestinal dysmotility and cachexia

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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