title: ATL1 and REEP1 mutations in hereditary and sporadic upper motor neuron syndromes.
abstract: SPAST mutations are the most common cause of autosomal dominant hereditary spastic paraplegias (AD-HSPs), but many spastic paraplegia patients are found to carry no mutations in this gene. In order to assess the contribution of ATL1 and REEP1 in AD-HSP, we performed mutational analysis in 27 SPAST-negative AD-HSP families. We found three novel ATL1 mutations and one REEP1 mutation in five index-patients. In 110 patients with sporadic adult-onset upper motor neuron syndromes, a novel REEP1 mutation was identified in one patient. Apart from a significantly younger age at onset in ATL1 patients and restless legs in some, the clinical phenotype of ATL1 and REEP1 was similar to other pure AD-HSPs.
authors.affiliation: Department of Neurology, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. ST.Bot@neuro.umcn.nl
authors.forename: S T
authors.initials: ST
authors.lastname: de Bot
authors.forename: J H
authors.initials: JH
authors.lastname: Veldink
authors.forename: S
authors.initials: S
authors.lastname: Vermeer
authors.forename: A R
authors.initials: AR
authors.lastname: Mensenkamp
authors.forename: F
authors.initials: F
authors.lastname: Brugman
authors.forename: H
authors.initials: H
authors.lastname: Scheffer
authors.forename: L H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: H P H
authors.initials: HP
authors.lastname: Kremer
authors.forename: E J
authors.initials: EJ
authors.lastname: Kamsteeg
authors.forename: B P
authors.initials: BP
authors.lastname: van de Warrenburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C495318:REEP1 protein, human; C440006:ATL1 protein, human; D019204:GTP-Binding Proteins