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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

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Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.

Depienne Christel C Fedirko Estelle E Forlani Sylvie S Cazeneuve Cécile C Ribaï Pascale P Feki Imed I Tallaksen Chantal C Nguyen Karine K Stankoff Bruno B Ruberg Merle M Stevanin Giovanni G Durr Alexandra A Brice Alexis A

Journal of medical genetics 20061110 4

<h4>Background</h4>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.<h4>Methods</h4>121 mutation-negative probands were screened for rearrangements in SPG4 by multiplex ligation-dependent probe amplification.<h4>Results</h4>24 patients with 16 different heterozygotic exon deletions in SPG4 (20%) were identified, ranging from one ...[more]

PMID: 17098887

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