SPG10 is a rare cause of spastic paraplegia in European families

Background: SPG10 is an autosomal dominant form of hereditary
spastic paraplegia (HSP), which is caused by mutations in the
neural kinesin heavy chain KIF5A gene, the neuronal motor of fast
anterograde axonal transport. Only four mutations have been
identified to date.Objective: To determine the frequency of SPG10
in European families with HSP and to specify the SPG10
phenotype.Patients and methods: 80 index patients from families
with autosomal dominant HSP were investigated for SPG10 mutations
by direct sequencing of the KIF5A motor domain. Additionally, the
whole gene was sequenced in 20 of these families.Results: Three
novel KIF5A mutations were detected in German families, including
one missense mutation (c.759G>T, p.K253N), one in frame deletion
(c.768_770delCAA, p.N256del) and one splice site mutation
(c.217G>A). Onset of gait disturbance varied from infancy to 30
years of age. All patients presented clinically with pure HSP, but
a subclinical sensory--motor neuropathy was detected by
neurophysiology studies.Conclusions: SPG10 accounts for
approximately 3% of European autosomal dominant HSP families. All
mutations affect the motor domain of kinesin and thus most likely
impair axonal transport. Clinically, SPG10 is characterised by
spastic paraplegia with mostly subclinical peripheral neuropathy.