Schimke immuno-osseous dysplasia: a cell autonomous disorder?

Am J Med Genet A. 2006 Feb 15;140(4):340-8. doi: 10.1002/ajmg.a.31089.


SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like protein 1) encodes a SWI/SNF ATP-dependent chromatin remodeling protein. Mutations in SMARCAL1 cause the autosomal-recessive multisystem disorder Schimke immuno-osseous dysplasia (SIOD); this suggests that the SMARCAL1 protein is involved in the development or maintenance of multiple organs. Disease within these many tissues could arise by a cell autonomous or a cell non-autonomous mechanism. Consistent with a cell autonomous mechanism, we did not find any disease recurrence in transplanted organs or protection of other tissues by the organ grafts. In order to better understand the role of SMARCAL1 during normal development and in the pathogenesis of SIOD, we characterized the spatial and temporal expression of the murine homolog (Smarcal1). The Smarcal1 mRNA and protein were expressed throughout development and in all tissues affected in patients with SIOD including the bone, kidney, thymus, thyroid, tooth, bone marrow, hair, eye, and blood vessels. Significantly, the expression profile of Smarcal1 in the mouse has led us to reexamine and identify novel pathology in our patient population resulting in changes in the clinical management of SIOD. The expression of Smarcal1 in affected tissues and the non-recurrence of disease in grafted organs lead us to hypothesize a cell autonomous function for SMARCAL1 and to propose tissue-specific mechanisms for the pathophysiology of SIOD.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Mice
  • Mutation*
  • Organ Specificity
  • Osteochondrodysplasias / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution


  • RNA, Messenger
  • SMARCAL1 protein, human
  • Smarcal1 protein, mouse
  • DNA Helicases