Gene deletions as frequent as mutations

In the most common form of HSP, the spastin gene (SPG4) which is responsible for 40% of AD-HSP, has been found with exon deletions as frequently as point mutations as the cause of HSP.

BackgroundPoint 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.


121 mutation-negative probands were screened for rearrangements in SPG4 by multiplex ligation-dependent probe amplification.


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.


Exon deletions in SPG4 are as frequent as point mutations, and SPG4 is responsible for 40% of AD-HSP.


J Med Genet. 2007 Apr;44(4):281-4. Epub 2006 Nov 10.
Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.
Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribaï P, Feki I, Tallaksen C, Nguyen K, Stankoff B, Ruberg M, Stevanin G, Durr A, Brice A.
PMID: 17098887 [PubMed – indexed for MEDLINE]