title: Genome-wide gene expression profiling and mutation analysis of Saudi patients with Canavan disease.
abstract: OBJECTIVE
  Canavan disease, caused by a deficiency of aspartoacylase, is one of the most common cerebral degenerative diseases of infancy. The aims of this study were to identify the mutations associated with Canavan disease in Saudi Arabia and to identify differentially expressed genes likely to contribute to the development of this disease.
  
  
  METHODS
  Polymerase chain reaction, long polymerase chain reaction, multiplex ligation-dependent probe amplification, sequencing, array comparative genomic hybridization (aCGH), and global gene expression profiling were used to determine putative mutations and likely gene signatures in cultured fibroblasts of patients from Saudi Arabia.
  
  
  RESULTS
  One novel and one known large deletion and two previously known mutations (IVS4 + 1G>T and G27R) were identified. Compared with controls, 1440 genes were significantly modulated in Canavan patients (absolute fold change [FC] > or =4). Genome-wide gene expression profiling results indicated that some genes, involved in apoptosis, muscle contraction and development, mitochondrial oxidation, inflammation and glutamate, and aspartate metabolism, were significantly dysregulated.
  
  
  CONCLUSIONS
  Our findings indicate that the presence of muscle weakness and hypotonia in patients may be associated with the dysregulated gene activities of cell motility, muscle contraction and development, actin binding, and cytoskeletal-related activities. Overall, these observations are in accordance with previous studies performed in a knockout mouse model.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. nkaya@kfshrc.edu.sa
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.forename: Faiqa
authors.initials: F
authors.lastname: Imtiaz
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Moeenaldeen
authors.initials: M
authors.lastname: Al-Sayed
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Odaib
authors.forename: Fatma
authors.initials: F
authors.lastname: Al-Zahrani
authors.forename: Bashayer R
authors.initials: BR
authors.lastname: Al-Mubarak
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Owain
authors.forename: Hesham
authors.initials: H
authors.lastname: Al-Dhalaan
authors.forename: Aziza
authors.initials: A
authors.lastname: Chedrawi
authors.forename: Zuhair
authors.initials: Z
authors.lastname: Al-Hassnan
authors.forename: Serdar
authors.initials: S
authors.lastname: Coskun
authors.forename: Nadia
authors.initials: N
authors.lastname: Sakati
authors.forename: Pinar
authors.initials: P
authors.lastname: Ozand
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
mesh_terms: D017825:Canavan Disease / Q000235:genetics*; D002478:Cells, Cultured; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D012529:Saudi Arabia; D017384:Sequence Deletion