Schimke immuno-osseous dysplasia: A cell autonomous disorder?

Leah I. Elizondo, Cheng Huang, Jennifer L. Northrop, Kimiko Deguchi, Johanna Marietta Clewing, Dawna L. Armstrong, Cornelius F. Boerkoel

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)340-348
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume140 A
Issue number4
StatePublished - Feb 15 2006


  • SF2 helicase
  • SNF2

ASJC Scopus subject areas

  • Genetics(clinical)


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