Browse by author
Lookup NU author(s): Professor Grainne Gorman, Joanna Stewart, Dr Mark Buddles, Professor Patrick Chinnery, Emeritus Professor Doug Turnbull, Professor Rita HorvathORCiD, Professor Robert Taylor
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Background: Mutations in the Twinkle (PEO1) gene are a recognized cause of autosomal dominant progressive external ophthalmoplegia (adPEO), resulting in the accumulation of multiple mitochondrial DNA (mtDNA) deletions and cytochrome c oxidase (COX)-deficient fibers in skeletal muscle secondary to a disorder of mtDNA maintenance. Patients typically present with isolated extraocular muscle involvement, with little apparent evidence of the clinical heterogeneity documented in other mtDNA maintenance disorders, in particular POLG-related disease. Methods: We reviewed the clinical, histochemical, and molecular genetics analysis of 33 unreported patients from 26 families together with all previous cases described in the literature to define the clinical phenotype associated with PEO1 mutations. Results: Ptosis and ophthalmoparesis were almost universal clinical features among this cohort, with 52%(17/33) reporting fatigue and 33%(11/33) having mild proximal myopathy. Features consistent with CNS involvement were rarely described; however, in 24% (8/33) of the patients, cardiac abnormalities were reported. Mitochondrial histochemical changes observed in muscle showed remarkable variability, as did the secondary mtDNA deletions, which in some patients were only detected by PCR-based assays and not Southern blotting. Moreover, we report 7 novel PEO1 variants. Conclusions: Our data suggest a shared clinical phenotype with variable mild multiorgan involvement, and that the contribution of PEO1 mutations as a cause of adPEO may well be underestimated. Direct sequencing of the PEO1 gene should be considered in adPEO patients prior to muscle biopsy. Neurology (R) 2010; 74: 1619-1626
Author(s): Fratter C, Gorman GS, Stewart JD, Buddles M, Smith C, Evans J, Seller A, Poulton J, Roberts M, Hanna MG, Rahman S, Omer SE, Klopstock T, Schoser B, Kornblum C, Czermin B, Lecky B, Blakely EL, Craig K, Chinnery PF, Turnbull DM, Horvath R, Taylor RW
Publication type: Article
Publication status: Published
Journal: Neurology
Year: 2010
Volume: 74
Issue: 20
Pages: 1619-1626
Print publication date: 01/05/2010
ISSN (print): 0028-3878
ISSN (electronic): 1526-632X
Publisher: Lippincott Williams & Wilkins
URL: http://dx.doi.org/10.1212/WNL.0b013e3181df099f
DOI: 10.1212/WNL.0b013e3181df099f
Altmetrics provided by Altmetric
