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A novel mitochondrial tRNA(Glu) (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle

Lookup NU author(s): Dr Charlotte Alston, Emeritus Professor Doug Turnbull, Professor Robert Taylor


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Mitochondrial respiratory chain defects are associated with diverse clinical phenotypes in both adults and children, and may be caused by mutations in either nuclear or mitochondrial DNA (mtDNA). We report the molecular genetic investigations of a patient with chronic progressive external ophthalmoplegia (CPEO) and myopathy where muscle biopsies taken 11 years apart revealed a progressive increase in the proportion of cytochrome c oxidase (COX)-deficient fibres. Mitochondrial genetic analysis of the early biopsy had seemingly excluded both mtDNA rearrangements and mtDNA point mutations. Sequencing mtDNA from individual COX-deficient muscle fibres in the second biopsy, however, identified an unreported m.14723 T>C substitution within the mitochondrial tRNA(Glu) (MTTE) gene, which fulfilled all canonical criteria for pathogenicity. The m.14723 T>C mutation was absent from several tissues, including muscle, from maternal relatives suggesting a de novo event, whilst quantitative analysis of the first muscle biopsy confirmed a very low level of the mutation (7% mutated mtDNA), highlighting a potential problem whereby pathogenic mtDNA mutations may remain undetected using established screening methodologies. (C) 2010 Elsevier B.V. All rights reserved.

Publication metadata

Author(s): Alston CL, Lowe J, Turnbull DM, Maddison P, Taylor RW

Publication type: Article

Publication status: Published

Journal: Journal of the Neurological Sciences

Year: 2010

Volume: 298

Issue: 1-2

Pages: 140-144

Print publication date: 31/08/2010

ISSN (print): 0022-510X

ISSN (electronic): 1878-5883

Publisher: Elsevier BV


DOI: 10.1016/j.jns.2010.08.014


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Funder referenceFunder name
UK National Commissioning Group
074454/Z/04/ZWellcome Trust