Abstract
SPG8 is a rare autosomal dominant hereditary spastic paraplegia (AD-HSP), with only six SPG8 families described so far. Our purpose was to screen for KIAA0196 (SPG8) mutations in AD-HSP patients and to investigate their phenotype. Extensive family investigation was performed after positive KIAA0196 mutation analysis, which was part of an on-going mutation screening effort in AD-HSP patients. A novel pathogenic KIAA0196 mutation p.(Gly696Ala) was identified in two AD-HSP patients, who subsequently were shown to belong to a single large Dutch pedigree with more than 10 affected family members. The phenotype consisted of a pure HSP with ages at onset between 20 and 60 years, distally reduced vibration sense in the legs in all, and urinary urgency in seven out of 10 patients. Frequent features were exercise- or emotion-induced increase of spasticity and gait problems and chronic nonspecific lower back and joint pains. We have identified a fourth pathogenic KIAA0196 mutation in a Dutch HSP-family, the seventh family worldwide, with a less severe clinical course than described before.
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Acknowledgments
We would like to thank the patients for their participation in this study. This work was supported by the European Community’s Seventh Framework Program FP7/2007-2013 under grant agreement n° 223143 (project acronym: TECHGENE) to HS.
Conflicts of interest
SdB, SV, WB, AH, MV, AV and EJK report no disclosures. BvdW receives or has received research support from the Prinses Beatrix Fonds, the European Union, the Brain Foundation, Ipsen Pharmaceuticals, the Grossweiler Foundation, and the Royal Dutch Society for Physical Therapy. BK receives or has received research support from the University Medical Centre Groningen, and the BCN-Brain Research Institute. HS receives or has received research support from the European Union and the Netherlands Organization for Health Research and Development (ZONMW).
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This study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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de Bot, S.T., Vermeer, S., Buijsman, W. et al. Pure adult-onset Spastic Paraplegia caused by a novel mutation in the KIAA0196 (SPG8) gene. J Neurol 260, 1765–1769 (2013). https://doi.org/10.1007/s00415-013-6870-x
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DOI: https://doi.org/10.1007/s00415-013-6870-x