title: Point mutations and a large intragenic deletion in SPG11 in complicated spastic paraplegia without thin corpus callosum.
abstract: BACKGROUND
  Hereditary spastic paraplegia (HSP) with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterised by slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the gene associated with the major locus involved, encodes spatacsin, a protein of unknown function.
  
  
  METHODS
  Different types of mutations were identified in patients with the complex form of HSP (cHSP) including TCC. We screened a series of 45 index patients with different types of cHSP with (n = 10) and without (n = 35) TCC.
  
  
  RESULTS
  Ten mutations, of which five are novel, were detected in seven patients. Of importance, three out of seven mutated patients present with cHSP without TCC. Among the novel mutations identified, we characterised a large intragenic rearrangement deleting 2.6 kb of the SPG11 gene. The rearrangement is due to non-allelic homologous recombination between Alu sequences flanking the breakpoints.
  
  
  CONCLUSIONS
  These findings expand the mutation spectrum of SPG11 and suggest that SPG11 mutations may occur more frequently in familial than sporadic forms of cHSP without TCC. This helps to define further clinical and molecular criteria for a correct diagnosis of the SPG11 related form of cHSP. In addition, the intragenic deletion detected here, and the mechanism involved, both provide clues to address the issue of SPG11 missing mutant alleles previously reported.
authors.forename: C
authors.initials: C
authors.lastname: Crimella
authors.forename: A
authors.initials: A
authors.lastname: Arnoldi
authors.forename: F
authors.initials: F
authors.lastname: Crippa
authors.forename: M L
authors.initials: ML
authors.lastname: Mostacciuolo
authors.forename: F
authors.initials: F
authors.lastname: Boaretto
authors.forename: M
authors.initials: M
authors.lastname: Sironi
authors.forename: M Grazia
authors.initials: MG
authors.lastname: D'Angelo
authors.forename: S
authors.initials: S
authors.lastname: Manzoni
authors.forename: L
authors.initials: L
authors.lastname: Piccinini
authors.forename: A C
authors.initials: AC
authors.lastname: Turconi
authors.forename: A
authors.initials: A
authors.lastname: Toscano
authors.forename: O
authors.initials: O
authors.lastname: Musumeci
authors.forename: S
authors.initials: S
authors.lastname: Benedetti
authors.forename: R
authors.initials: R
authors.lastname: Fazio
authors.forename: N
authors.initials: N
authors.lastname: Bresolin
authors.forename: A
authors.initials: A
authors.lastname: Daga
authors.forename: A
authors.initials: A
authors.lastname: Martinuzzi
authors.forename: M T
authors.initials: MT
authors.lastname: Bassi
mesh_terms: D061085:Agenesis of Corpus Callosum; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis / Q000379:methods; D021901:DNA, Intergenic / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology
chemical_list: D021901:DNA, Intergenic; D011506:Proteins; C520412:SPG11 protein, human