Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement

We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A.

Source: Journal of Child Neurology - July 11, 2016 Category: Neurology Authors: Hotchkiss, L., Donkervoort, S., Leach, M. E., Mohassel, P., Bharucha-Goebel, D. X., Bradley, N., Nguyen, D., Hu, Y., Gurgel-Giannetti, J., Bönnemann, C. G. Tags: Original Articles Source Type: research