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
Statistics from Altmetric.com
Published Online First 10 November 2006
Competing interests: None declared.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.