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.

• Authors: Christel Depienne, Estelle Fedirko, Sylvie Forlani, Cécile Cazeneuve, Pascale Ribaï, Imed Feki, Chantal Tallaksen, Karine Nguyen, Bruno Stankoff, Merle Ruberg, Giovanni Stevanin, Alexandra Durr, Alexis Brice
• Journal: Journal of medical genetics (J Med Genet) Vol. 44 Issue 4 Pg. 281-4 (Apr 2007) ISSN: 1468-6244 [Electronic] England
• PMID: 17098887 (Publication Type: Comparative Study, Letter, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine Triphosphatases
• Spastin
• SPAST protein, human

Topics

• Adenosine Triphosphatases (deficiency, genetics)
• Adolescent
• Adult
• Age of Onset
• Aged
• Child
• Child, Preschool
• DNA Mutational Analysis
• Exons (genetics)
• Female
• France (epidemiology)
• Genetic Heterogeneity
• Genetic Testing
• Humans
• Infant
• Male
• Middle Aged
• Point Mutation
• Polymerase Chain Reaction (methods)
• Portugal (epidemiology)
• Spain (epidemiology)
• Spastic Paraplegia, Hereditary (epidemiology, genetics)
• Spastin