Background: Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). Standard methods for genetic analyses miss, however, exonic microdeletions.
Objective and Methods: We screened 121 mutation-negative probands for rearrangements in SPG4 by multiplex ligation-dependent probe amplification (MLPA).
Results: We identified 24 patients with 16 different heterozygous exon deletions in SPG4 (20%) ranging from one exon to the whole coding sequence. Comparison with 78 patients with point mutations showed a similar clinical picture but earlier age at onset.
Conclusions: These results indicate that exon deletions in SPG4 are as frequent as point mutations and that SPG4 is responsible for 40% of AD-HSP.