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.

SUBMITTER: Depienne C 

PROVIDER: S-EPMC2598038 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature