title: Autosomal recessive hereditary spastic paraplegia with thin corpus callosum among Saudis.
abstract: OBJECTIVE
  To assess the mutational and clinical spectrum of spatacsin associated with autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC).
  
  
  METHODS
  A retrospective study was carried out at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from February 2008 until March 2011. Four unrelated Saudi Arabian families with ARHSP-TCC were studied, totaling 13 affected individuals. Clinical presentations included gait disturbance at variable ages (2-18 years), spastic paraplegia with mild to moderate cognitive impairment and evidence of peripheral neuropathy in 2 families. Brain MRI showed TCC accompanied by periventricular white matter changes and cortical atrophy.
  
  
  RESULTS
  A genome wide scan demonstrated linkage to the SPG11 locus. Sequencing revealed 4 mutations. The first is an insertion/deletion (indel) consisting of a 3 base pair (bp) deletion and 23 bp insertion (L1268L fsX), the second is a one bp deletion (S1923R fsX), and the third and the fourth are nonsense mutations (Q341X and R651X). All mutations predict premature truncation of the spatacsin protein.
  
  
  CONCLUSIONS
  We report 2 novel mutations in this gene, including an indel considerably larger than any other identified to date. The identification of these mutations further confirms the causative link between SPG11 and ARHSP-TCC in these families.
authors.affiliation: Departments of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.forename: Hatem N
authors.initials: HN
authors.lastname: Murad
authors.forename: Batoul M
authors.initials: BM
authors.lastname: Baz
authors.forename: Samiya T
authors.initials: ST
authors.lastname: Hagos
authors.forename: Rana A
authors.initials: RA
authors.lastname: Al-Amr
authors.forename: Suad A
authors.initials: SA
authors.lastname: Al-Yamani
authors.forename: Salem M
authors.initials: SM
authors.lastname: Al-Wadaee
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.forename: Saeed A
authors.initials: SA
authors.lastname: Bohlega
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics*; D018912:Arabs; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D018389:Codon, Nonsense / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D003337:Corpus Callosum / Q000473:pathology*; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006801:Humans; D008279:Magnetic Resonance Imaging; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D012529:Saudi Arabia; D017384:Sequence Deletion / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000097:blood / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D011506:Proteins; C520412:SPG11 protein, human