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Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia
  1. Christel Depienne1,2,3,
  2. Estelle Fedirko2,
  3. Sylvie Forlani1,
  4. Cécile Cazeneuve2,
  5. Pascale Ribaï1,2,
  6. Imed Feki1,
  7. Chantal Tallaksen1,
  8. Karine Nguyen4,
  9. Bruno Stankoff5,
  10. Merle Ruberg1,
  11. Giovanni Stevanin1,2,3,
  12. Alexandra Durr1,2,3,
  13. Alexis Brice1,2,3,5
  1. 1INSERM U679 (formerly U289), Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  2. 2Département de Génétique, Cytogénétique et Embryologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  3. 3Université Pierre et Marie Curie - Paris VI, Paris, France
  4. 4Hôpital de la Timone, Marseille, France
  5. 5Fédération des Maladies du Système Nerveux, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
  1. Correspondence to:
 A Brice
 INSERM U679, Groupe Hospitalier Pitié-Salpêtrière, 47 Boulevard de l’Hôpital, 75013 Paris, France; brice{at}


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.

  • AD-HSP, autosomal dominant hereditary spastic paraplegia
  • HSP, hereditary spastic paraplegia
  • MLPA, multiplex ligation-dependent probe amplification

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  • Published Online First 10 November 2006

  • Competing interests: None declared.