title: Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia.
abstract: BACKGROUND
  Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogenous disorder reported in Quebec caused by mutations in the SACS gene (chromosome 13q12). Recently, we identified a Tunisian kindred demonstrating linkage to the ARSACS locus.
  
  
  OBJECTIVE
  To report clinical, neurophysiological, and nerve biopsy findings in patients with autosomal recessive cerebellar ataxia related to the SACS gene in Tunisia.
  
  
  METHODS
  Genetic linkage analysis of patients with early-onset autosomal recessive cerebellar ataxia allowed the identification of 4 families from which 18 patients demonstrated linkage to the ARSACS locus. The patients were evaluated according to the International Cooperative Ataxia Rating Scale. Peripheral nerve conduction, sensory evoked potentials, and nerve biopsy were performed in most patients.
  
  
  RESULTS
  The mean age at onset was 4.5 years. The clinical phenotype was stereotyped and associated with a progressive cerebellar syndrome, a pyramidal syndrome with brisk knee reflexes, and Babinski sign and absent ankle reflexes. The course of the disease varied among patients. Sensory evoked potentials showed severe posterior column involvement. Peripheral nerve investigations demonstrated axonal and demyelinating neuropathy. Four mutations, 2 missense and 2 nonsense, were found.
  
  
  CONCLUSIONS
  In Tunisia, autosomal recessive cerebellar ataxia related to the SACS gene demonstrated a homogenous phenotype and heterogeneous allelic mutations.
authors.affiliation: Department of Neurology, National Institute of Neurology, Tunis, Tunisia.
authors.forename: Ghada
authors.initials: G
authors.lastname: El Euch-Fayache
authors.forename: Irfan
authors.initials: I
authors.lastname: Lalani
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
authors.forename: Ilhem
authors.initials: I
authors.lastname: Turki
authors.forename: Karim
authors.initials: K
authors.lastname: Ouahchi
authors.forename: Wu-Yen
authors.initials: WY
authors.lastname: Hung
authors.forename: Samir
authors.initials: S
authors.lastname: Belal
authors.forename: Teepu
authors.initials: T
authors.lastname: Siddique
authors.forename: Faycal
authors.initials: F
authors.lastname: Hentati
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005073:Evoked Potentials, Somatosensory; D005074:Evoked Potentials, Visual; D005260:Female; D005808:Genes, Recessive; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009431:Neural Conduction; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D010543:Peroneal Nerve / Q000473:pathology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013132:Spinocerebellar Degenerations / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D014416:Tunisia
chemical_list: D006360:Heat-Shock Proteins; C404403:SACS protein, human