Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia
- Christel Depienne1,2,3,
- Estelle Fedirko2,
- Sylvie Forlani1,
- Cécile Cazeneuve2,
- Pascale Ribaï1,2,
- Imed Feki1,
- Chantal Tallaksen1,
- Karine Nguyen4,
- Bruno Stankoff5,
- Merle Ruberg1,
- Giovanni Stevanin1,2,3,
- Alexandra Durr1,2,3,
- Alexis Brice1,2,3,5
- 1INSERM U679 (formerly U289), Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- 2Département de Génétique, Cytogénétique et Embryologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- 3Université Pierre et Marie Curie - Paris VI, Paris, France
- 4Hôpital de la Timone, Marseille, France
- 5Fédération des Maladies du Système Nerveux, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Correspondence to: A Brice INSERM U679, Groupe Hospitalier Pitié-Salpêtrière, 47 Boulevard de l’Hôpital, 75013 Paris, France; brice{at}ccr.jussieu.fr
- Received 13 September 2006
- Accepted 19 October 2006
- Revised 16 October 2006
- Published Online First 10 November 2006
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.
- AD-HSP, autosomal dominant hereditary spastic paraplegia
- HSP, hereditary spastic paraplegia
- MLPA, multiplex ligation-dependent probe amplification
Footnotes
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Published Online First 10 November 2006
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Competing interests: None declared.
