Novel SPG11 mutations in Chinese families with hereditary spastic paraplegia with thin corpus callosum

Abstract

Background: Hereditary spastic paraplegia is a clinically and genetically heterogeneous neurodegenerative disorder characterized by progressive spasticity of the lower limbs. Mutations in SPG11 gene have been recently identified as a major cause of hereditary spastic paraplegia with thin corpus callosum.

Methods: Two unrelated Chinese families were examined by clinical evaluation, mutation analysis of SPG11, detailed neuropsychological assessment and diffusion tensor imaging.

Results: Both patients presented with spastic paraparesis and learning disability. Two novel and one known mutations in SPG11 were detected through genetic analysis. Cognitive impairment was found with severe deficits in domains such as executive functions and memory. Magnetic resonance imaging showed thin corpus callosum while diffusion tensor imaging revealed increased mean diffusion and decreased fractional anisotropy in the corpus callosum and subcortical white matter in frontal, temporal lobe compared with the healthy controls.

Conclusions: This study widens the spectrum of mutations in SPG11. The application of detailed neuropsychological tests and diffusion tensor imaging could detect cerebral subtle involvement even in early stage of the disease.