HSP caused by deletions rather than mutations is missed in standard gene tests.
Exon deletions in SPG4 as a cause of HSP are as frequent as point mutations, but are missed in standard gene tests.
SPG4 is far and away the most common cause of HSP, being responsible for 40% of AD-HSP.
BACKGROUND: Point mutations in SPG4, the gene encoding spastin, are a known frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). However, standard methods for genetic analyses miss exonic microdeletions.
METHODS: We screened 121 mutation-negative probands for rearrangements in SPG4.
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.
J Med Genet. 2006 Nov 10
Exon Deletions of SPG4 are a Frequent Cause of Hereditary Spastic Paraplegia.
Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribai P, Feki I, Tallaksen C, Nguyen K, Stankoff B, Ruberg M, Stevanin G, Durr A, Brice A.
INSERM U679, France.