Neurogenetics

, Volume 6, Issue 3, pp 151–158

Identification of a VPS13A founder mutation in French Canadian families with chorea-acanthocytosis

  • 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
Original Article

DOI: 10.1007/s10048-005-0220-9

Cite this article as:
Dobson-Stone, C., Velayos-Baeza, A., Jansen, A. et al. Neurogenetics (2005) 6: 151. doi:10.1007/s10048-005-0220-9

Abstract

Mutations in VPS13A cause chorea-acanthocytosis (ChAc), an autosomal recessive neurodegenerative disorder. VPS13A is located in a tail-to-tail arrangement with GNA14 on chromosome 9q21. ChAc shows substantial 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 homozygous 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 consanguineous 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 carriers 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

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Carol Dobson-Stone
    • 1
    • 9
  • Antonio Velayos-Baeza
    • 1
  • An Jansen
    • 2
  • Frederick Andermann
    • 2
  • François Dubeau
    • 2
  • Francine Robert
    • 3
  • Anne Summers
    • 4
  • Anthony E. Lang
    • 5
  • Sylvain Chouinard
    • 6
  • Adrian Danek
    • 7
  • Eva Andermann
    • 8
  • Anthony P. Monaco
    • 1
  1. 1.The Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK
  2. 2.Department of Neurology and NeurosurgeryMcGill University, and the Montreal Neurological Hospital and InstituteMontrealCanada
  3. 3.Genetics Program, North Bay & District Health UnitNorth BayCanada
  4. 4.Medical Genetics, North York General Hospital, Department of PaediatricsUniversity of TorontoTorontoCanada
  5. 5.Division of NeurologyUniversity of TorontoTorontoCanada
  6. 6.André-Barbeau Movement Disorders UnitUniversity of MontrealMontrealCanada
  7. 7.Neurologische KlinikLudwig-Maximilians-UniversitätMunichGermany
  8. 8.Department of Neurology and Neurosurgery, and Department of Human GeneticsMcGill University, and the Montreal Neurological Hospital and InstituteMontrealCanada
  9. 9.The Garvan Institute of Medical ResearchUniversity of New South WalesSydneyAustralia

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