Hereditary Spastic Paraplegia 3A Associated With Axonal Neuropathy

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Abstract
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by a progressive gait disturbance due to lower-extremity spasticity and weakness. In the pure HSP forms, the phenotype is restricted to spasticity while in the complex forms additional features such as peripheral neuropathy, mental retardation, or distal amyotrophy are present.1 Autosomal dominant HSP accounts for more than 80% of all familial cases, and the most common subtype (40%) is SPG4 due to spastin mutations.1 Approximately 10% of autosomal dominant HSP families harbor mutations in SPG3A, encoding atlastin. Thus far, 22 distinct mutations have been reported in SPG3A. In the present study, we performed a mutation screening of the SPG3A gene in a large cohort of 182 unrelated patients with pure or complex forms of HSP in whom SPG4 mutations had been excluded. We identified 12 different SPG3A mutations, of which 7 are novel, and we report the related genetic, clinical, electrophysiological, and pathological findings.