title: SPG11 compound mutations in spastic paraparesis with thin corpus callosum.
abstract: BACKGROUND
  Autosomal recessive hereditary spastic paraparesis with thin corpus callosum (ARHSP-TCC) is being increasingly recognized as a variety of spastic paraplegia with mental retardation. SPG11 gene mutations have been reported to be associated with ARHSP-TCC.
  
  
  METHODS
  As an independent group, we investigated SPG11 gene involvement in four individuals not previously described with either recessive or sporadic HSP-TCC presentation.
  
  
  RESULTS
  Chromosome 15q13-15 segregating autosomal disease haplotypes were different across the kindreds and sequencing of SPG11 identified four novel frameshift/nonsense segregating mutations and the R2034X mutation, which were in heterozygous compound status. The affected examined had decreased thalamic and bilateral paracentral frontal lobe metabolism on (18)F-flurodeoxyglucose PET.
  
  
  CONCLUSIONS
  Loss-of-function SPG11 mutations are the major cause of autosomal recessive hereditary spastic paraparesis with thin corpus callosum in Southern Europe, even in apparently sporadic cases. Decreased thalamic metabolism was consistently a phenotypical SPG11 mutation hallmark.
authors.affiliation: Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), Pío XII 55, 31008-Pamplona (Navarra), Spain.
authors.forename: L
authors.initials: L
authors.lastname: Samaranch
authors.forename: M
authors.initials: M
authors.lastname: Riverol
authors.forename: J C
authors.initials: JC
authors.lastname: Masdeu
authors.forename: E
authors.initials: E
authors.lastname: Lorenzo
authors.forename: J M
authors.initials: JM
authors.lastname: Vidal-Taboada
authors.forename: J
authors.initials: J
authors.lastname: Irigoyen
authors.forename: M A
authors.initials: MA
authors.lastname: Pastor
authors.forename: P
authors.initials: P
authors.lastname: de Castro
authors.forename: P
authors.initials: P
authors.lastname: Pastor
mesh_terms: D000328:Adult; D061085:Agenesis of Corpus Callosum; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003337:Corpus Callosum / Q000000981:diagnostic imaging / Q000378:metabolism; D004252:DNA Mutational Analysis; D004734:Energy Metabolism / Q000235:genetics; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005787:Gene Frequency; D005808:Genes, Recessive / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D020336:Paraparesis, Spastic / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011877:Radionuclide Imaging; D013030:Spain; D013577:Syndrome; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D005819:Genetic Markers; D011506:Proteins; C520412:SPG11 protein, human