Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation

J Med Genet. 2009 Jan;46(1):49-59. doi: 10.1136/jmg.2008.060095. Epub 2008 Sep 19.


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.

Conclusion: Our results show for the first time that SMARCAL1 binds chromatin in vivo and that SIOD arises from impairment of diverse SMARCAL1 functions.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cells, Cultured
  • DNA Helicases / analysis
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Deletion
  • Genes, Recessive
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Osteochondrodysplasias / genetics*
  • Phenotype
  • RNA, Messenger / metabolism
  • Sequence Alignment


  • RNA, Messenger
  • SMARCAL1 protein, human
  • Adenosine Triphosphatases
  • DNA Helicases