title: Clinical and molecular characterization of ataxia with oculomotor apraxia patients in Saudi Arabia.
abstract: BACKGROUND
  Autosomal recessive ataxias represent a group of clinically overlapping disorders. These include ataxia with oculomotor apraxia type1 (AOA1), ataxia with oculomotor apraxia type 2 (AOA2) and ataxia-telangiectasia-like disease (ATLD). Patients are mainly characterized by cerebellar ataxia and oculomotor apraxia. Although these forms are not quite distinctive phenotypically, different genes have been linked to these disorders. Mutations in the APTX gene were reported in AOA1 patients, mutations in SETX gene were reported in patients with AOA2 and mutations in MRE11 were identified in ATLD patients. In the present study we describe in detail the clinical features and results of genetic analysis of 9 patients from 4 Saudi families with ataxia and oculomotor apraxia.
  
  
  METHODS
  This study was conducted in the period between 2005-2010 to clinically and molecularly characterize patients with AOA phenotype. Comprehensive sequencing of all coding exons of previously reported genes related to this disorder (APTX, SETX and MRE11).
  
  
  RESULTS
  A novel nonsense truncating mutation c.6859 C > T, R2287X in SETX gene was identified in patients from one family with AOA2. The previously reported missense mutation W210C in MRE11 gene was identified in two families with autosomal recessive ataxia and oculomotor apraxia.
  
  
  CONCLUSIONS
  Mutations in APTX , SETX and MRE11 are common in patients with autosomal recessive ataxia and oculomotor apraxia. The results of the comprehensive screening of these genes in 4 Saudi families identified mutations in SETX and MRE11 genes but failed to identify mutations in APTX gene.
authors.affiliation: Department of Neurosciences, King Faisal Specialist Hospital and Research Center, Riaydh, Saudi Arabia.
authors.forename: Saeed A
authors.initials: SA
authors.lastname: Bohlega
authors.forename: Jameela M
authors.initials: JM
authors.lastname: Shinwari
authors.forename: Latifa J
authors.initials: LJ
authors.lastname: Al Sharif
authors.forename: Dania S
authors.initials: DS
authors.lastname: Khalil
authors.forename: Thamer S
authors.initials: TS
authors.lastname: Alkhairallah
authors.forename: Nada A
authors.initials: NA
authors.lastname: Al Tassan
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001072:Apraxias / Q000235:genetics; D001260:Ataxia Telangiectasia / Q000235:genetics; D001483:Base Sequence; D002524:Cerebellar Ataxia / Q000151:congenital; D002874:Chromosome Mapping; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D004265:DNA Helicases; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D034141:Hypoalbuminemia / Q000235:genetics; D000076228:MRE11 Homologue Protein; D008297:Male; D064251:Multifunctional Enzymes; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D020365:RNA Helicases / Q000235:genetics*; D012529:Saudi Arabia; D020754:Spinocerebellar Ataxias / Q000151:congenital; D013132:Spinocerebellar Degenerations / Q000235:genetics; D055815:Young Adult
chemical_list: C438188:APTX protein, human; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D064251:Multifunctional Enzymes; D009687:Nuclear Proteins; D004247:DNA; D000076228:MRE11 Homologue Protein; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases