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Neurogenetics
Published in: neurogenetics 1/2006

01-03-2006 | Original Article

Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia

Authors: Marcia A. Blair, Shaochun Ma, Peter Hedera

Published in: Neurogenetics | Issue 1/2006

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Abstract

Autosomal dominant hereditary spastic paraplegia (AD HSP) linked to chromosome 12q (SPG10) is caused by mutations in the neuronal kinesin heavy-chain KIF5A gene. This is a rare cause of AD HSP, and only two disease-causing mutations have been reported thus far. In both instances, affected individuals harboring mutations in the KIF5A gene displayed symptom onset at a very early age. Here we present the results of clinical and genetic analyses of a large kindred with uncomplicated AD HSP. We were able to establish a definitive linkage to the SPG10 locus, and sequencing of the KIF5A gene revealed a heterozygous missense mutation 1,035 A>G in exon 10, resulting in tyrosine-to-cysteine substitution. This mutation is located in a highly conserved kinesin motor domain of the neuronal kinesin heavy-chain protein, but in contrast to two previously reported missense mutations, the age of symptom onset in our family was much later, with an average age of 36.1±4 years. Our results demonstrate that mutations in the KIF5A gene can also be associated with an adult age of onset of AD HSP.
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Metadata
Title
Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia
Authors
Marcia A. Blair
Shaochun Ma
Peter Hedera
Publication date
01-03-2006
Publisher
Springer-Verlag
Published in
Neurogenetics / Issue 1/2006
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-005-0027-8

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