title: Pure adult-onset spastic paraplegia caused by a novel mutation in the KIAA0196 (SPG8) gene.
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.
authors: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands. ST.Bot@neuro.umcn.nl
authors: Susanne T
authors: ST
authors: de Bot
authors: Sascha
authors: S
authors: Vermeer
authors: Wendy
authors: W
authors: Buijsman
authors: Angelien
authors: A
authors: Heister
authors: Marsha
authors: M
authors: Voorendt
authors: Aad
authors: A
authors: Verrips
authors: Hans
authors: H
authors: Scheffer
authors: Hubertus P H
authors: HP
authors: Kremer
authors: Bart P C
authors: BP
authors: van de Warrenburg
authors: Erik-Jan
authors: EJ
authors: Kamsteeg
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D011506:Proteins; C517003:WASHC5 protein, human