Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure

Bohlega, S.; Van Goethem, G.; Al Semari, A.; Löfgren, A.; Al Hamed, M.; Van Broeckhoven, C.; Kambouris, M.

doi:10.1016/j.nmd.2009.10.002

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Volume 19, Issue 12 , Pages 845-848, December 2009

Novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia and multisystem failure

S. Bohlega
- Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Corresponding author. Address: Section of Neurology, Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Tel.: +966 1 464 7272x32819/32772.
G. Van Goethem
- Department of Neurology, University Hospital Antwerp, Antwerpen, Belgium
- Laboratory of Neurogenetics, Institute Born-Bunge, Antwerpen, Belgium
- Department of Molecular Genetics, VIB, Antwerpen, Belgium
A. Al Semari
- Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
A. Löfgren
- Laboratory of Neurogenetics, Institute Born-Bunge, Antwerpen, Belgium
- Department of Molecular Genetics, VIB, Antwerpen, Belgium
- Department of Medical Genetics, University of Antwerp, Antwerpen, Belgium
M. Al Hamed
- Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
C. Van Broeckhoven
- Laboratory of Neurogenetics, Institute Born-Bunge, Antwerpen, Belgium
- Department of Molecular Genetics, VIB, Antwerpen, Belgium
- Department of Medical Genetics, University of Antwerp, Antwerpen, Belgium
M. Kambouris
- Research Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Received 12 May 2009; received in revised form 29 August 2009; accepted 2 October 2009.

Abstract

A Saudi Arabian family presented with adult onset autosomal dominant progressive external ophthalmoplegia (adPEO) complicated by late onset reversible failure of the CNS, respiratory, hepatic, and endocrine systems. Clinical findings were suggestive of mitochondrial dysfunction and multiple mitochondrial DNA deletions were demonstrated on long range and real time polymerase chain reaction assays but not on Southern blotting. The disorder is caused by a novel heterozygous PEO1 mutation predicting a Leu360Gly substitution in the twinkle protein. The peculiar clinical presentation expands the variable phenotype observed in adPEO and Twinkle gene mutations.

Keywords: mtDNA, PEO, PEO1, Twinkle gene, Mutation, adPEO