1. ¹Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland
2. ²Department of Neurology, Columbia University Medical Center, New York, USA
3. ³Murdoch Children's Research Institute, Royal Children's Hospital and Department of Paediatrics, University of Melbourne, Melbourne, Australia
4. ⁴Department of Neurology, Institute of Clinical Medicine, University of Bergen & Haukeland University Hospital, Bergen, Norway
5. ⁵Division of Neurology and the Neuromuscular Reference Center, University Hospital Antwerp, Belgium
6. ⁶Department of Molecular Genetics, Neurogenetics group, VIB and University of Antwerp, Belgium
7. ⁷Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

Correspondence: Professor A Suomalainen, Research Program of Molecular Neurology, Biomedicum-Helsinki, r. C523b, University of Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland. Tel: +358 9 4717 1965; Fax: +358 9 4717 1964; E-mail:anu.wartiovaara@helsinki.fi

Received 29 November 2006; Revised 19 February 2007; Accepted 7 March 2007; Published online 11 April 2007.

Abstract

We reported previously that the DNA polymerase (POLG) W748S mutation, a common cause of mitochondrial recessive ataxia syndrome (MIRAS), has a common ancient founder for all the disease chromosomes in Finland, Norway, United Kingdom, and Belgium. Here, we present results showing that the same ancestral chromosome underlies MIRAS and Alpers syndrome in Australia and New Zealand. Furthermore, we show that a second common POLG mutation, A467T, also shows common European ancestry: patients from Australia, New Zealand, and the United States share a common haplotype with the previously reported European patients. These data of ancestral haplotypes indicate that the POLG locus is quite stable and that the recessive W748S and A467T mutations, and probably also G848S, have occurred once in history. They have effectively spread to populations of European descent with carrier frequencies up to 1% in several populations. Our data predict that these mutations are common causes of ataxia and Alpers disease in the Western world.