title: Alu elements mediate large SPG11 gene rearrangements: further spatacsin mutations.
abstract: OBJECTIVE
  Hereditary spastic paraplegias compose a group of neurodegenerative disorders with a large clinical and genetic heterogeneity. Among the autosomal recessive forms, spastic paraplegia type 11 is the most common.
  
  
  METHODS
  To better understand the spastic paraplegia type 11 mutation spectrum, we studied a group of 54 patients with hereditary spastic paraplegia. Mutation screening was performed by PCR amplification of SPG11 coding regions and intron boundaries, followed by sequencing. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  We report 13 families with spastic paraplegia type 11 carrying either novel or previously identified mutations. We describe a complex entire SPG11 rearrangement and show that large gene rearrangements are frequent among patients with spastic paraplegia type 11. Moreover, we mapped the deletion breakpoints of three different large SPG11 deletions and provide evidence for Alu microhomology-mediated exon deletion.
  
  
  CONCLUSIONS
  Our analysis shows that the high number of repeated elements in SPG11 together with the presence of recombination hotspots and the high intrinsic instability of the 15q locus all contribute toward making this genomic region more prone to large gene rearrangements. These findings enlarge the amount of data relating repeated elements with neurodegenerative disorders and highlight their importance in human disease and genome evolution.
authors.affiliation: UnIGENe, IBMC, Porto, Portugal.
authors.forename: Maria
authors.initials: M
authors.lastname: Conceição Pereira
authors.forename: José Leal
authors.initials: JL
authors.lastname: Loureiro
authors.forename: Jorge
authors.initials: J
authors.lastname: Pinto-Basto
authors.forename: Eva
authors.initials: E
authors.lastname: Brandão
authors.forename: Ana
authors.initials: A
authors.lastname: Margarida Lopes
authors.forename: Georgina
authors.initials: G
authors.lastname: Neves
authors.forename: Pureza
authors.initials: P
authors.lastname: Dias
authors.forename: Ruth
authors.initials: R
authors.lastname: Geraldes
authors.forename: Isabel Pavão
authors.initials: IP
authors.lastname: Martins
authors.forename: Vitor Tedim
authors.initials: VT
authors.lastname: Cruz
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Kamsteeg
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Paula
authors.initials: P
authors.lastname: Coutinho
authors.forename: Jorge
authors.initials: J
authors.lastname: Sequeiros
authors.forename: Isabel
authors.initials: I
authors.lastname: Alonso
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D020087:Alu Elements; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D005091:Exons; D005260:Female; D023061:Gene Order; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*; D055815:Young Adult
chemical_list: D011506:Proteins; C520412:SPG11 protein, human