1. Exon deletions of SPG4 are a frequent cause of hereditary spastic paraplegia.
- Author
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Depienne C, Fedirko E, Forlani S, Cazeneuve C, Ribaï P, Feki I, Tallaksen C, Nguyen K, Stankoff B, Ruberg M, Stevanin G, Durr A, and Brice A
- Subjects
- Adenosine Triphosphatases deficiency, Adolescent, Adult, Age of Onset, Aged, Child, Child, Preschool, DNA Mutational Analysis, 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, Spastin, Adenosine Triphosphatases genetics, Exons genetics, Spastic Paraplegia, Hereditary genetics
- 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.
- Published
- 2007
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