Neurogenetics (2005) 6: 151–158 DOI 10.1007/s10048-005-0220-9 ORIGINAL ARTICLE Carol Dobson-Stone . Antonio Velayos-Baeza . An Jansen . Frederick Andermann . François Dubeau . Francine Robert . Anne Summers . Anthony E. Lang . Sylvain Chouinard . Adrian Danek . Eva Andermann . Anthony P. Monaco Identification of a VPS13A founder mutation in French Canadian families with chorea-acanthocytosis Received: 5 April 2005 / Accepted: 27 April 2005 / Published online: 26 May 2005 # Springer-Verlag 2005 Abstract Mutations in VPS13A cause chorea-acantho- cytosis (ChAc), an autosomal recessive neurodegenerative disorder. VPS13A is located in a tail-to-tail arrangement with GNA14 on chromosome 9q21. ChAc shows substan- tial allelic heterogeneity, with no single VPS13A mutation causing the majority of cases. We examined 11 patients in four French Canadian ChAc pedigrees for mutations in VPS13A. Affected members of three families were homo- zygous for a 37-kb deletion of the four terminal exons of VPS13A (EX70_EX73del). This deletion also encompasses the two terminal exons of GNA14. Two affected females in family 4 were homozygous for the splicing mutation 4242+ 1G>T. Remarkably, the affected males in this highly con- sanguineous pedigree were compound heterozygotes for EX70_EX73del and 4242+1G>T. PCR analysis of the deletion breakpoint junction revealed that an additional patient with French Canadian ancestry was heterozygous for the EX70_EX73del allele. The identification of a common 9q21 haplotype associated with EX70_EX73del in at least four apparently unrelated ChAc families implies that ChAc shows a founder effect in French Canadians, and that routine testing for EX70_ EX73del in suspected ChAc cases may therefore be worthwhile in this population. The deletion breakpoint PCR described here will enable rapid identification of both homozygous and heterozygous car- riers of EX70_EX73del. Keywords Neuroacanthocytosis . Founder effect . DNA mutational analysis . Nucleic acid repetitive sequences . G alpha subunit 14 Abbreviations ChAc: chorea-acanthocytosis . DHPLC: denaturing high-performance liquid chromatography . FRAM: free right-arm monomer . MER: medium reiteration frequency element . OPMD: oculopharyngeal muscular dystrophy . SNP: single nucleotide polymorphism C. Dobson-Stone . A. Velayos-Baeza . A. P. Monaco (*) The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK e-mail: anthony.monaco@well.ox.ac.uk Tel.: +44-1865-287502 Fax: +44-1865-287650 A. Jansen . F. Andermann . F. Dubeau Department of Neurology and Neurosurgery, McGill University, and the Montreal Neurological Hospital and Institute, Montreal, Canada F. Robert Genetics Program, North Bay & District Health Unit, North Bay, Canada A. Summers Medical Genetics, North York General Hospital, Department of Paediatrics, University of Toronto, Toronto, Canada A. E. Lang Division of Neurology, University of Toronto, Toronto, Canada S. Chouinard André-Barbeau Movement Disorders Unit, University of Montreal, Montreal, Canada A. Danek Neurologische Klinik, Ludwig-Maximilians-Universität, Munich, Germany E. Andermann Department of Neurology and Neurosurgery, and Department of Human Genetics, McGill University, and the Montreal Neurological Hospital and Institute, Montreal, Canada C. Dobson-Stone The Garvan Institute of Medical Research, University of New South Wales, Sydney, Australia