title: Hereditary spastic paraplegia with mental impairment and thin corpus callosum in Tunisia: SPG11, SPG15, and further genetic heterogeneity.
abstract: OBJECTIVE
  To perform a clinical and genetic study of Tunisian families with autosomal recessive (AR) hereditary spastic paraplegia with thin corpus callosum (HSP-TCC).
  
  
  METHODS
  Linkage studies and mutation screening.
  
  
  METHODS
  Reference Center for Neurogenetics in South and Center Tunisia.
  
  
  METHODS
  Seventy-three subjects from 33 "apparently" unrelated Tunisian families with AR HSP.
  
  
  METHODS
  Families with AR HSP-TCC were subsequently tested for linkage to the corresponding loci using microsatellite markers from the candidate intervals, followed by direct sequencing of the KIAA1840 gene in families linked to SPG11.
  
  
  RESULTS
  We identified 8 Tunisian families (8 of 33 [24%]), including 19 affected patients, fulfilling the clinical criteria for HSP-TCC. In 7 families, linkage to either SPG11 (62.5%) or SPG15 (25%) was suggested by haplotype reconstruction and positive logarithm of odds score values for microsatellite markers. The identification of 2 recurrent mutations (R2034X and M245VfsX) in the SPG11 gene in 5 families validated the linkage results. The neurological and radiological findings in SPG11 and SPG15 patients were relatively similar. The remaining family, characterized by an earlier age at onset and the presence of cataracts, was excluded for linkage to the 6 known loci, suggesting further genetic heterogeneity.
  
  
  CONCLUSIONS
  Autosomal recessive HSP-TCC is a frequent subtype of complicated HSP in Tunisia and is clinically and genetically heterogeneous. SPG11 and SPG15 are the major loci for this entity, but at least another genetic form with unique clinical features exists.
authors.affiliation: Department of Neurology, Habib Bourguiba University Hospital, Tunis, Tunisia.
authors.forename: Amir
authors.initials: A
authors.lastname: Boukhris
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Imed
authors.initials: I
authors.lastname: Feki
authors.forename: Elodie
authors.initials: E
authors.lastname: Denis
authors.forename: Nizar
authors.initials: N
authors.lastname: Elleuch
authors.forename: Mohamed Imed
authors.initials: MI
authors.lastname: Miladi
authors.forename: Jérémy
authors.initials: J
authors.lastname: Truchetto
authors.forename: Paola
authors.initials: P
authors.lastname: Denora
authors.forename: Samir
authors.initials: S
authors.lastname: Belal
authors.forename: Chokri
authors.initials: C
authors.lastname: Mhiri
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D061085:Agenesis of Corpus Callosum; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000150:complications / Q000235:genetics / Q000473:pathology; D014416:Tunisia / Q000453:epidemiology
chemical_list: D011506:Proteins; C520412:SPG11 protein, human