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Characterization of a novel SPG3A deletion in a French‐Canadian family
Author(s) -
Meijer Inge A.,
Dion Patrick,
Laurent Sandra,
Dupré Nicolas,
Brais Bernard,
Levert Annie,
Puymirat Jacques,
Rioux Marie France,
Sylvain Michel,
Zhu PengPeng,
Soderblom Cynthia,
Stadler Julia,
Blackstone Craig,
Rouleau Guy A.
Publication year - 2007
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21114
Subject(s) - hereditary spastic paraplegia , genetics , triphosphatase , spasticity , gene , biology , mutation , phenotype , guanosine , medicine , physical medicine and rehabilitation
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. Ann Neurol 2007