title: Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.
abstract: BACKGROUND
  Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). However, standard methods for genetic analyses fail to detect exonic microdeletions.
  
  
  METHODS
  121 mutation-negative probands were screened for rearrangements in SPG4 by multiplex ligation-dependent probe amplification.
  
  
  RESULTS
  24 patients with 16 different heterozygotic exon deletions in SPG4 (20%) were identified, ranging from one exon to the whole coding sequence. Comparison with 78 patients with point mutations showed a similar clinical picture but an earlier age at onset.
  
  
  CONCLUSIONS
  Exon deletions in SPG4 are as frequent as point mutations, and SPG4 is responsible for 40% of AD-HSP.
authors.forename: Christel
authors.initials: C
authors.lastname: Depienne
authors.forename: Estelle
authors.initials: E
authors.lastname: Fedirko
authors.forename: Sylvie
authors.initials: S
authors.lastname: Forlani
authors.forename: Cécile
authors.initials: C
authors.lastname: Cazeneuve
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaï
authors.forename: Imed
authors.initials: I
authors.lastname: Feki
authors.forename: Chantal
authors.initials: C
authors.lastname: Tallaksen
authors.forename: Karine
authors.initials: K
authors.lastname: Nguyen
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.forename: Merle
authors.initials: M
authors.lastname: Ruberg
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011174:Portugal / Q000453:epidemiology; D013030:Spain / Q000453:epidemiology; D015419:Spastic Paraplegia, Hereditary / Q000453:epidemiology / Q000235:genetics*; D000074181:Spastin
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human