title: Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.
abstract: BACKGROUND
  Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive pleiotropic disorder caused by mutations in SMARCAL1. SMARCAL1 encodes an enzyme with homology to the SNF2 chromatin remodelling proteins.
  
  
  METHODS
  To assess the affect of SMARCAL1 mutations associated with SIOD on SMARCAL1 expression and function, we characterised the effects of various mutations on mRNA and protein expression in patient tissues and cell lines, and the ATPase activity, subcellular localisation, and chromatin binding of SMARCAL1 missense mutants.
  
  
  RESULTS
  The SIOD associated SMARCAL1 mutations affected SMARCAL1 protein expression, stability, subcellular localisation, chromatin binding, and enzymatic activity. Further, expressing SMARCAL1 missense mutants in Drosophila melanogaster showed that disease severity was inversely proportionate to overall SMARCAL1 activity.
  
  
  CONCLUSIONS
  Our results show for the first time that SMARCAL1 binds chromatin in vivo and that SIOD arises from impairment of diverse SMARCAL1 functions.
authors.forename: L I
authors.initials: LI
authors.lastname: Elizondo
authors.forename: K S
authors.initials: KS
authors.lastname: Cho
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Yan
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: K
authors.initials: K
authors.lastname: Choi
authors.forename: E A
authors.initials: EA
authors.lastname: Sloan
authors.forename: K
authors.initials: K
authors.lastname: Deguchi
authors.forename: S
authors.initials: S
authors.lastname: Lou
authors.forename: A
authors.initials: A
authors.lastname: Baradaran-Heravi
authors.forename: H
authors.initials: H
authors.lastname: Takashima
authors.forename: T
authors.initials: T
authors.lastname: Lücke
authors.forename: F A
authors.initials: FA
authors.lastname: Quiocho
authors.forename: C F
authors.initials: CF
authors.lastname: Boerkoel
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005808:Genes, Recessive; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D012333:RNA, Messenger; C412482:SMARCAL1 protein, human; D000251:Adenosine Triphosphatases; D004265:DNA Helicases