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

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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.

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Authors and Affiliations

  1. Département de Génétique et Cytogénétique, U.F. de Neurogénétique, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    Cécile Cazeneuve, Channkanira Sân, Eric LeGuern & Alexis Brice

  2. Department of Pediatrics, Faculty of Medicine, University of Khartoum, Khartoum, Sudan

    Salah A. Ibrahim

  3. Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan

    Maowia M. Mukhtar

  4. Department of Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan

    Musa M. Kheir

  5. INSERM UMR_S 679 Neurologie & Thérapeutique Expérimentale, Groupe Hospitalier Pitié-Salpêtrière, Paris, France

    Eric LeGuern & Alexis Brice

  6. UMR_S679, UPMC Univ Paris 06, Paris, France

    Eric LeGuern & Alexis Brice

  7. Division of Pediatric Neurology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Mustafa A. Salih

Authors
  1. Cécile Cazeneuve
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  2. Channkanira Sân
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  3. Salah A. Ibrahim
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  4. Maowia M. Mukhtar
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  5. Musa M. Kheir
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  6. Eric LeGuern
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  7. Alexis Brice
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  8. Mustafa A. Salih
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Correspondence to Cécile Cazeneuve.

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Cazeneuve, C., Sân, C., Ibrahim, S.A. et al. A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease. Neurogenetics 10, 265–270 (2009). https://doi.org/10.1007/s10048-009-0174-4

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  • DOI: https://doi.org/10.1007/s10048-009-0174-4

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