Journal Article

Spectrum of <i>SPG4</i> mutations in autosomal dominant spastic paraplegia

Nùria Fonknechten, Delphine Mavel, Paula Byrne, Claire-Sophie Davoine, Corinne Cruaud, Dominikus Boentsch, Delphine Samson, Paula Coutinho, Michael Hutchinson, Paul Mc Monagle, Jean-Marc Burgunder, Antonio Tartaglione, Olivier Heinzlef, Imed Feki, Thomas Deufel, Nollaig Parfrey, Alexis Brice, Bertrand Fontaine, Jean-François Prud’homme, Jean Weissenbach, Alexandra Dürr and Jamilé Hazan

in Human Molecular Genetics

Volume 9, issue 4, pages 637-644
Published in print March 2000 | ISSN: 0964-6906
Published online March 2000 | e-ISSN: 1460-2083 | DOI:
Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia

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Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by pro‐ gressive spasticity of the lower limbs. Five AD‐HSP loci have been mapped to chromosomes 14q, 2p, 15q, 8q and 12q. The SPG4 locus at 2p21–p22 has been shown to account for ∼40% of all AD‐HSP families. SPG4 encoding spastin, a putative nuclear AAA protein, has recently been identified. Here, sequence analysis of the 17 exons of SPG4 in 87 unrelated AD‐HSP patients has resulted in the detection of 34 novel mutations. These SPG4 mutations are scattered along the coding region of the gene and include all types of DNA modification including missense (28%), nonsense (15%) and splice site point (26.5%) mutations as well as deletions (23%) and insertions (7.5%). The clinical analysis of the 238 mutation carriers revealed a high proportion of both asymptomatic carriers (14/238) and patients unaware of symptoms (45/238), and permitted the redefinition of this frequent form of AD-HSP.

Journal Article.  5329 words.  Illustrated.

Subjects: Genetics and Genomics

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