Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations

S. Winterthun, G. Ferrari, L. He, R. W. Taylor, M. Zeviani, D. M. Turnbull, B. A. Engelsen, G. Moen, Laurence A. Bindoff

Research output: Contribution to journalArticle

Abstract

Objective: To investigate three families and one sporadic case with a recessively inherited ataxic syndrome. Methods: Clinical and genetic studies were performed in six individuals. Southern blotting and real time PCR were used to detect deletions of mtDNA and mutations in the POLG gene were identified using a combination of DHPLC and direct DNA sequencing. Results: The patients have a distinctive, progressive disorder that starts with episodic symptoms such as migraine-like headache or epilepsy. Ataxia, which is a combination of central and peripheral disease, develops later as does ophthalmoplegia. The commonest form of epilepsy was focal and involved the occipital lobes. Myoclonus was common and patients have a high risk of status epilepticus. MRI typically shows signal changes in the central cerebellum, olivary nuclei, occipital cortex, and thalami. COX negative muscle fibers were found in four of six; in one patient these were rare and in another absent. Multiple mtDNA deletions were identified in all patients, although in two these were not apparent on Southern blotting and real time PCR was required to demonstrate the defect. Two families were homozygous for a previously described POLG mutation, G1399A (A467T). One family and the sporadic case had the same two new mutations, a G to C at position 1491 (Q497H) and a G to C at 2243 (W748S). Conclusions: Mutations in POLG cause a recessively inherited syndrome with episodic features and progressive ataxia. Characteristic changes on MRI are seen and although skeletal muscle may appear morphologically normal, multiple mtDNA deletions can be detected using real-time PCR.

Original languageEnglish
Pages (from-to)1204-1208
Number of pages5
JournalNeurology
Volume64
Issue number7
Publication statusPublished - Apr 12 2005

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Mitochondrial DNA
Real-Time Polymerase Chain Reaction
Occipital Lobe
Mutation
Ataxia
Southern Blotting
Olivary Nucleus
Ophthalmoplegia
Myoclonus
Partial Epilepsy
Status Epilepticus
Sequence Deletion
Migraine Disorders
Thalamus
DNA Sequence Analysis
Cerebellum
Epilepsy
Skeletal Muscle
Muscles
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Winterthun, S., Ferrari, G., He, L., Taylor, R. W., Zeviani, M., Turnbull, D. M., ... Bindoff, L. A. (2005). Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations. Neurology, 64(7), 1204-1208.

Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations. / Winterthun, S.; Ferrari, G.; He, L.; Taylor, R. W.; Zeviani, M.; Turnbull, D. M.; Engelsen, B. A.; Moen, G.; Bindoff, Laurence A.

In: Neurology, Vol. 64, No. 7, 12.04.2005, p. 1204-1208.

Research output: Contribution to journalArticle

Winterthun, S, Ferrari, G, He, L, Taylor, RW, Zeviani, M, Turnbull, DM, Engelsen, BA, Moen, G & Bindoff, LA 2005, 'Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations', Neurology, vol. 64, no. 7, pp. 1204-1208.
Winterthun S, Ferrari G, He L, Taylor RW, Zeviani M, Turnbull DM et al. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations. Neurology. 2005 Apr 12;64(7):1204-1208.
Winterthun, S. ; Ferrari, G. ; He, L. ; Taylor, R. W. ; Zeviani, M. ; Turnbull, D. M. ; Engelsen, B. A. ; Moen, G. ; Bindoff, Laurence A. / Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase γ mutations. In: Neurology. 2005 ; Vol. 64, No. 7. pp. 1204-1208.
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