Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia.
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.
Blair
Marcia A
MA
Department of Neurology, Vanderbilt University, Nashville, TN 37232-8552, USA.
Ma
Shaochun
S
Hedera
Peter
P
D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
C500506:KIF5A protein, human; D016547:Kinesins