Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.
Journal of Medical Genetics. 2007-04-01; 44(4): 281-284
DOI: 10.1136/jmg.2006.046425
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1. 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.
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.
DOI: 10.1136/jmg.2006.046425
PMCID: PMC2598038
PMID: 17098887 [Indexed for MEDLINE]