The expanding phenotype of MELAS caused by the m.3291T > C mutation in the MT-TL1 gene

E Keilland¹, C A Rupar², Asuri N Prasad³, K Y Tay⁴, A Downie⁵, C Prasad⁶

Affiliations

¹ Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
² Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Department of Biochemistry, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
³ Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Department of Neurology, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
⁴ Medical Imaging, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
⁵ Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Paediatric Psychology, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
⁶ Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.

PMID: 27014580
PMCID: PMC4789386
DOI: 10.1016/j.ymgmr.2016.02.003

Case Reports

The expanding phenotype of MELAS caused by the m.3291T > C mutation in the MT-TL1 gene

E Keilland et al. Mol Genet Metab Rep. 2016.

. 2016 Feb 22:6:64-9.

doi: 10.1016/j.ymgmr.2016.02.003. eCollection 2016 Mar.

Authors

E Keilland¹, C A Rupar², Asuri N Prasad³, K Y Tay⁴, A Downie⁵, C Prasad⁶

Affiliations

¹ Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
² Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Department of Biochemistry, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
³ Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Department of Neurology, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
⁴ Medical Imaging, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
⁵ Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Paediatric Psychology, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.
⁶ Department of Pediatrics, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Children's Health Research Institute, Children's Hospital London Health Sciences Centre, London, Ontario, Canada; Western University, Children's Hospital London Health Sciences Centre, London, Ontario, Canada.

PMID: 27014580
PMCID: PMC4789386
DOI: 10.1016/j.ymgmr.2016.02.003

Abstract

m.3291T > C mutation in the MT-TL1 gene has been infrequently encountered in association with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), however remains poorly characterized from a clinical perspective. In the following report we describe in detail the phenotypic features, long term follow up (> 7 years) and management in a Caucasian family with MELAS due to the m.3291T > C mutation and review the literature on m.3291T > C mutation. The clinical phenotype in the proposita included overlapping features of MELAS, MERRF (Myoclonic epilepsy and ragged-red fiber syndrome), MNGIE (Mitochondrial neurogastrointestinal encephalopathy), KSS (Kearns-Sayre Syndrome) and CPEO (Chronic progressive external ophthalmoplegia).

Keywords: MELAS; MELAS 3291T > C; Mitochondrial; Phenotypic features; tRNAleu (UUR) mutation.

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Figures

**Fig. 1**
Showing Pedigree with multiple affected individuals.

**Fig. 2**
Proposita with bilateral ptosis.

**Fig. 3**
Axial FLAIR (Fluid Attenuation Inversion Recovery, figure A) sequence shows multiple areas of brain parenchymal high signal (long white arrow) in the temporal lobes bilaterally and the right occipital lobe. FLAIR image 4 years later (figure B) reveals an old infarct in the right temporal lobe (white arrowheads) but the other areas of signal abnormalities have returned to normal.

**Fig. 4**
Single voxel MR spectroscopy (TE144) obtained at the same time as figure A showed the characteristic inverted doublet of lactate within one of the areas of abnormality.

**Fig. 5**
Overlapping Mitochondrial syndromes. (The patient described in the report has many of the features of the clinical phenotypes encountered in MERFF, CPEO, KSS, MELAS, and MNGIE).

See this image and copyright information in PMC

References

1. Pavlakis S.G. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann. Neurol. 1984;16(4):481–488. - PubMed
1. Finsterer J. Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation. Acta Neurol. Scand. 2007;116(1):1–14. - PubMed
1. Goto Y. A new point mutation at nucleotide pair 3291 of the mitochondrial tRNA(Leu(UUR)) gene in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) Biochem. Biophys. Res. Commun. 1994;202(3):1624–1630. - PubMed
1. Mitomap Mutations Database (2011). Available from: http://www.mitomap.org/.
1. Human Mitochondrial Genome Database (2005). Available from: http://www.mtdb.igp.uu.se.

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The expanding phenotype of MELAS caused by the m.3291T > C mutation in the MT-TL1 gene

Affiliations

The expanding phenotype of MELAS caused by the m.3291T > C mutation in the MT-TL1 gene

Authors

Affiliations

Abstract

Figures

References

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LinkOut - more resources

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