title: Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia.
abstract: BACKGROUND
  Autosomal recessive cerebellar ataxias (ARCA) are a complex group of neurodegenerative disorders with great genetic and phenotypic heterogeneity, over 30 genes/loci have been associated with more than 20 different clinical forms of ARCA. Genetic heterogeneity combined with highly variable clinical expression of the cerebellar symptoms and overlapping features complicate furthermore the etiological diagnosis of ARCA. The determination of the most frequent mutations and corresponding ataxias, as well as particular features specific to a population, are mandatory to facilitate and speed up the diagnosis process, especially when an appropriate treatment is available.
  
  
  METHODS
  We explored 166 patients (115 families) refered to the neurology units of Algiers central hospitals (Algeria) with a cerebellar ataxia phenotype segregating as an autosomal recessive pattern of inheritance. Genomic DNA was extracted from peripheral blood samples and mutational screening was performed by PCR and direct sequencing or by targeted genomic capture and massive parallel sequencing of 57 genes associated with inherited cerebellar ataxia phenotypes.
  
  
  RESULTS
  In this work we report the clinical and molecular results obtained on a large cohort of Algerian patients (110 patients/76 families) with genetically determined autosomal recessive ataxia, representing 9 different types of ARCA and 23 different mutations, including 6 novel ones. The five most common ARCA in this cohort were Friedreich ataxia, ataxia with isolated vitamin E deficiency, ataxia with oculomotor apraxia type 2, autosomal recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1.
  
  
  CONCLUSIONS
  We report here a large cohort of patients with genetically determined autosomal recessive ataxia and the first study of the genetic context of ARCA in Algeria. This study showed that in Algerian patients, the two most common types of ataxia (Friedreich ataxia and ataxia with isolated vitamin E deficiency) coexist with forms that may be less common or underdiagnosed. To refine the genotype/phenotype correlation in rare and heteregeneous diseases as autosomal recessive ataxias, more extensive epidemiological investigations and reports are necessary as well as more accurate and detailed clinical characterizations. The use of standardized clinical and molecular protocols would thus enable a better knowledge of the different forms of ARCA.
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, USTHB, Alger, Algeria. hamza_wahiba@hotmail.fr.
authors.forename: Wahiba
authors.initials: W
authors.lastname: Hamza
authors.affiliation: Service de Neurologie, CHU Mustapha Bacha, Alger, Algeria. miapacha@yahoo.fr.|Laboratoire de Neurosciences, Université d'Alger 1, Alger, Algeria. miapacha@yahoo.fr.
authors.forename: Lamia
authors.initials: L
authors.lastname: Ali Pacha
authors.affiliation: Laboratoire de Neurosciences, Université d'Alger 1, Alger, Algeria. tarikhamadouche@gmail.com.|Laboratoire de Biologie Moléculaire, Faculté des Sciences, UMBB, Boumerdes, Algeria. tarikhamadouche@gmail.com.
authors.forename: Tarik
authors.initials: T
authors.lastname: Hamadouche
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/Université de Strasbourg UMR7104, INSERM U964, Illkirch, France. jmuller@igbmc.fr.|Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. jmuller@igbmc.fr.
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/Université de Strasbourg UMR7104, INSERM U964, Illkirch, France. drouot@igbmc.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Drouot
authors.affiliation: Service de Neurologie, CHU Ben Aknoun, Alger, Algeria. ferratfarida@yahoo.fr.
authors.forename: Farida
authors.initials: F
authors.lastname: Ferrat
authors.affiliation: Service de Neurologie, EHS Ali Aït Idir, Alger, Algeria. makrisamira@yahoo.fr.
authors.forename: Samira
authors.initials: S
authors.lastname: Makri
authors.affiliation: Service de Neurologie, CHU Ben Aknoun, Alger, Algeria. chaouch_malika@hotmail.com.
authors.forename: Malika
authors.initials: M
authors.lastname: Chaouch
authors.affiliation: Service de Neurologie, CHU Mustapha Bacha, Alger, Algeria. meriemtazir@yahoo.com.|Laboratoire de Neurosciences, Université d'Alger 1, Alger, Algeria. meriemtazir@yahoo.com.
authors.forename: Meriem
authors.initials: M
authors.lastname: Tazir
authors.affiliation: Laboratoire de Génétique de Maladies Rares, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU de Montpellier, Montpellier, France. michel.koenig@inserm.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, USTHB, Alger, Algeria. trakibenhassine@hotmail.com.
authors.forename: Traki
authors.initials: T
authors.lastname: Benhassine
mesh_terms: D000293:Adolescent; D000328:Adult; D000462:Algeria / Q000453:epidemiology; D002524:Cerebellar Ataxia / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D023281:Genomics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D040582:Inheritance Patterns; D008297:Male; D009154:Mutation; D010641:Phenotype; D055815:Young Adult