OBJECTIVE We report a multigenerational family with uncomplicated hereditary spastic paraplegia type 4 and apparent anticipation. Genetic analysis of the proband revealed a frame shift mutation (5 base pair deletion) in exon 9 of the SPG4 gene encoding the spastin protein. We hypothesized that this deletion mutation may be dynamic and variability in the size of the deletion could account for th...

Kif5A is a neuronally-enriched isoform of the Kinesin-1 family of cellular transport motors. 23 separate mutations in the motor domain of Kif5A have been identified in patients with the complicated form of hereditary spastic paraplegia (HSP). We performed in vitro assays on dimeric recombinant Kif5A with HSP-causing mutations in the Switch I domain, which participates in the coordination and hy...

Complicated hereditary spastic paraplegia (HSP) presents with complex neurological and nonneurological manifestations. We report a patient with autosomal recessive (AR) HSP in whom laboratory investigations revealed hypobetalipoproteinemia raising the possibility of a shared pathophysiology of these clinical features. A lipid profile of his parents disclosed a normal maternal lipid profile. How...

Hereditary spastic paraplegia (HSP) is a group of genetically-determined disorders characterized by progressive spasticity and weakness of lower limbs. An apparently sporadic case of adult-onset spastic paraplegia is a frequent clinical problem and a significant proportion of cases are likely to be of genetic origin. HSP is clinically divided into pure and complicated forms. The later present w...

BACKGROUND Pelizaeus-Merzbacher disease (PMD) and a complicated form of familial spastic paraparesis (spastic paraplegia 2 [SPG2]) are X-linked development disorders of myelin formation caused by a mutation in the proteolipid protein (PLP) gene. Spastic paraplegia 2 is allelic to PMD. The wide range of PLP mutations results in a corresponding large spectrum of clinical severity in PMD, with a c...

The AP-5 complex is a recently identified but evolutionarily ancient member of the family of heterotetrameric adaptor proteins (AP complexes). It is associated with two proteins that are mutated in patients with hereditary spastic paraplegia, SPG11 and SPG15. Here we show that the four AP-5 subunits can be coimmunoprecipitated with SPG11 and SPG15, both from cytosol and from detergent-extracted...