title: A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson's disease.
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.
authors.affiliation: Département de Génétique et Cytogénétique, U.F. de Neurogénétique, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. cecile.cazeneuve@psl.aphp.fr
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: Channkanira
authors.initials: C
authors.lastname: Sân
authors.forename: Salah A
authors.initials: SA
authors.lastname: Ibrahim
authors.forename: Maowia M
authors.initials: MM
authors.lastname: Mukhtar
authors.forename: Musa M
authors.initials: MM
authors.lastname: Kheir
authors.forename: Eric
authors.initials: E
authors.lastname: Leguern
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Salih
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D013397:Sudan; D055815:Young Adult; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase