Short Communication

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 CazeneuveAffiliated withDépartement de Génétique et Cytogénétique, U.F. de Neurogénétique, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Email author 
  • , Channkanira SânAffiliated withDépartement de Génétique et Cytogénétique, U.F. de Neurogénétique, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière
  • , Salah A. IbrahimAffiliated withDepartment of Pediatrics, Faculty of Medicine, University of Khartoum
  • , Maowia M. MukhtarAffiliated withInstitute of Endemic Diseases, University of Khartoum
  • , Musa M. KheirAffiliated withDepartment of Medicine, Faculty of Medicine, University of Khartoum
  • , Eric LeGuernAffiliated withDépartement de Génétique et Cytogénétique, U.F. de Neurogénétique, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-SalpêtrièreINSERM UMR_S 679 Neurologie & Thérapeutique Expérimentale, Groupe Hospitalier Pitié-SalpêtrièreUMR_S679, UPMC Univ Paris 06
  • , Alexis BriceAffiliated withDépartement de Génétique et Cytogénétique, U.F. de Neurogénétique, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-SalpêtrièreINSERM UMR_S 679 Neurologie & Thérapeutique Expérimentale, Groupe Hospitalier Pitié-SalpêtrièreUMR_S679, UPMC Univ Paris 06
  • , Mustafa A. SalihAffiliated withDivision of Pediatric Neurology, College of Medicine, King Saud University

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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 disease Autosomal recessive PINK1 PARK6 Complex rearrangement Fork Stalling and Template Switching