neurogenetics

, Volume 10, Issue 3, pp 265–270

A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease

  • Cécile Cazeneuve
  • Channkanira Sân
  • Salah A. Ibrahim
  • Maowia M. Mukhtar
  • Musa M. Kheir
  • Eric LeGuern
  • Alexis Brice
  • Mustafa A. Salih
Short Communication

DOI: 10.1007/s10048-009-0174-4

Cite this article as:
Cazeneuve, C., Sân, C., Ibrahim, S.A. et al. Neurogenetics (2009) 10: 265. doi:10.1007/s10048-009-0174-4

Abstract

PARK2 and PINK1 gene mutations are involved in recessive early onset Parkinson’s disease (EOPD). In order to determine the causative mutations in three affected sibs from a consanguineous Sudanese family with EOPD, multiplex ligation-dependent probe amplification was performed and revealed that the patients were homozygous for a deletion of PINK1 exons 4 to 8. Breakpoint analysis revealed a complex rearrangement combining a large deletion and the insertion of a sequence duplicated from the DDOST gene intron 2, located near the PINK1 gene. As breakpoint sequences displayed only three base pairs of homology, this rearrangement may result from Fork Stalling and Template Switching mechanism. This third large rearrangement of PINK1 enlarges the mutation spectrum and, together with recent published data in Tunisian patients with EOPD, points out that PINK1 gene analysis, including search for large rearrangement, should be considered in early onset recessive PD patients, particularly those from Arab origin.

Keywords

Early onset Parkinson’s diseaseAutosomal recessivePINK1PARK6Complex rearrangementFork Stalling and Template Switching

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Cécile Cazeneuve
    • 1
  • Channkanira Sân
    • 1
  • Salah A. Ibrahim
    • 2
  • Maowia M. Mukhtar
    • 3
  • Musa M. Kheir
    • 4
  • Eric LeGuern
    • 1
    • 5
    • 6
  • Alexis Brice
    • 1
    • 5
    • 6
  • Mustafa A. Salih
    • 7
  1. 1.Département de Génétique et Cytogénétique, U.F. de NeurogénétiqueAssistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-SalpêtrièreParisFrance
  2. 2.Department of Pediatrics, Faculty of MedicineUniversity of KhartoumKhartoumSudan
  3. 3.Institute of Endemic DiseasesUniversity of KhartoumKhartoumSudan
  4. 4.Department of Medicine, Faculty of MedicineUniversity of KhartoumKhartoumSudan
  5. 5.INSERM UMR_S 679 Neurologie & Thérapeutique ExpérimentaleGroupe Hospitalier Pitié-SalpêtrièreParisFrance
  6. 6.UMR_S679UPMC Univ Paris 06ParisFrance
  7. 7.Division of Pediatric Neurology, College of MedicineKing Saud UniversityRiyadhSaudi Arabia