Neurologic phenotype of schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1

Kimiko Deguchi, Johanna Marietta Clewing, Leah I. Elizondo, Ryuki Hirano, Cheng Huang, Kunho Choi, Emily A. Sloan, Thomas Lücke, Katja M. Marwedel, Ralph D. Powell, Karen Santa Cruz, Sandrine Willaime-Morawek, Ken Inoue, Shu Lou, Jennifer L. Northrop, Yonehiro Kanemura, Derek Van Der Kooy, Hideyuki Okano, Dawna L. Armstrong, Cornelius F. Boerkoel

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Schimke immuno-osseous dysplasia (OMIM 242900) is an uncommon autosomal-recessive multisystem disease caused by mutations in SMARCAL1 (swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), a gene encoding a putative chromatin remodeling protein. Neurologic manifestations identified to date relate to enhanced atherosclerosis and cerebrovascular disease. Based on a clinical survey, we determined that half of Schimke immuno-osseous dysplasia patients have a small head circumference, and 15% have social, language, motor, or cognitive abnormalities. Postmortem examination of 2 Schimke immuno-osseous dysplasia patients showed low brain weights and subtle brain histologic abnormalities suggestive of perturbed neuron-glial migration such as heterotopia, irregular cortical thickness, incomplete gyral formation, and poor definition of cortical layers. We found that SMARCAL1 is highly expressed in the developing and adult mouse and human brain, including neural precursors and neuronal lineage cells. These observations suggest that SMARCAL1 deficiency may influence brain development and function in addition to its previously recognized effect on cerebral circulation.

Original languageEnglish (US)
Pages (from-to)565-577
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Issue number6
StatePublished - Jun 2008


  • Immunodeficiency
  • Microcephaly
  • Neural stem cell
  • Neuronal migration
  • Renal disease
  • Skeletal dysplasia

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)


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