Characterization of a novel SPG3A deletion in a French-Canadian family.

Abstract

Hereditary spastic paraplegias (HSPs) are characterized by progressive lower limb spasticity and weakness. Mutations in the SPG3A gene, which encodes the large guanosine triphosphatase atlastin, are the second most common cause of autosomal dominant hereditary spastic paraplegia. In a large SPG3A screen of 70 hereditary spastic paraplegia subjects, a novel in-frame deletion, p.del436N, was identified. Characterization of this deletion showed that it affects neither the guanosine triphosphatase activity of atlastin nor interactions between atlastin and spastin. Interestingly, immunoblot analysis of lymphoblasts from affected patients demonstrated a significant reduction in atlastin protein levels, supporting a loss-of-function disease mechanism.

• Authors: Inge A Meijer, Patrick Dion, Sandra Laurent, Nicolas Dupré, Bernard Brais, Annie Levert, Jacques Puymirat, Marie France Rioux, Michel Sylvain, Peng-Peng Zhu, Cynthia Soderblom, Julia Stadler, Craig Blackstone, Guy A Rouleau
• Journal: Annals of neurology (Ann Neurol) Vol. 61 Issue 6 Pg. 599-603 (Jun 2007) ISSN: 0364-5134 [Print] United States
• PMID: 17427918 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• RNA, Messenger
• ATL1 protein, human
• GTP Phosphohydrolases
• GTP-Binding Proteins

Topics

• Adolescent
• Adult
• Child, Preschool
• DNA Mutational Analysis
• Electrodiagnosis
• Family
• GTP Phosphohydrolases (analysis, genetics)
• GTP-Binding Proteins
• Humans
• Lymphocytes (chemistry)
• Membrane Proteins
• Middle Aged
• Paraplegia (diagnosis, genetics)
• Quebec
• RNA, Messenger (analysis)
• Sequence Deletion (genetics)
• Two-Hybrid System Techniques