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

By K. Deguchi, J.M. Clewing, L.I. Elizondo, R. Hirano, C. Huang, K. Choi, E.A. Sloan, T. Lucke, K.M. Marwedel, R. Powell, K. SantaCruz, Y. Fujita, S. Willaime-Morawek, K. Inoue, S. Lou, J. Northrop, Y. Kanemura, D. van der Kooy, H. Okano, D.L. Armstrong and C.F. Boerkoel


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

Topics: RB, RC0321
Year: 2008
OAI identifier:
Provided by: e-Prints Soton

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  4. (1961). Autoradiographic study of the cell migration during histogenesis of the cerebral cortex in the mouse. Nature
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  7. (2003). Cajal-Retzius cells, inhibitory interneuronal populations and neuropeptide Y expression in focal cortical dysplasia and microdysgenesis. Acta Neuropathol (Berl)
  8. (2007). Cerebellar atrophy in Schimkeimmuno-osseous dysplasia.
  9. (1989). Cerebrocortical microdysgenesis in neurologically normal subjects: A histopathologic study.
  10. Cloning and characterization of HARP/SMARCAL1: A prokaryotic HepA-related SNF2 helicase protein from human and mouse.
  11. (1985). Developmental dyslexia: Four consecutive patients with cortical anomalies. Ann Neurol
  12. (1985). Developmental expression of 2¶,3¶-cyclic nucleotide 3¶-phosphohydrolase in dissociated fetal rat brain cultures and rat brain.
  13. (1968). Differenzierungssto ¨rungen bei Epilepsie Jarbuch
  14. (2004). Disguising adult neural stem cells. Curr Opin Neurobiol
  15. (2002). Evaluation of in vitro proliferative activity of human fetal neural stem/progenitor cells using indirect measurements of viable cells based on cellular metabolic activity.
  16. (2004). Generalized atherosclerosis sparing the transplanted kidney in Schimke disease. Pediatr Nephrol
  17. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science
  18. (2004). Genetic basis of developmental malformations of the cerebral cortex. Arch Neurol
  19. (1987). Genetic counselling and antenatal diagnosis after the birth of an affected child.
  20. (2001). High-yield selection and extraction of two promoter-defined phenotypes of neural stem cells from the fetal human brain.
  21. (2003). Identification of chromatin-related protein interactions using protein microarrays. Proteomics
  22. (2006). Identification of multiple distinct Snf2 subfamilies with conserved structural motifs. Nucleic Acids Res
  23. Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice.
  24. (2000). Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature.
  25. (2001). Mechanisms of size control.
  26. (1999). Microcephaly with simplified gyral pattern in six related children.
  27. (1988). Microdysgenesis in resected temporal neocortex: Incidence and clinical significance in focal epilepsy.
  28. (1998). Microlissencephaly: A heterogeneous malformation of cortical development.
  29. (1972). Mode of cell migration to the superficial layers of fetal monkey neocortex.
  30. (2001). Molecular genetics of human microcephaly.
  31. (1985). Morphological aspects of aetiology and the course of infantile spasms (West-syndrome). Neuropediatrics
  32. (1996). Mouse-Musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev Biol
  33. (2006). Musashi1 antigen expression in human fetal germinal matrix development. Exp Neurol
  34. (2000). Musashi1: An evolutionally conserved marker for CNS progenitor cells including neural stem cells. Dev Neurosci
  35. (2002). Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.
  36. (2003). Neurogenesis and the cell cycle. Neuron
  37. (2000). Neuronal migration disorders: From genetic diseases to developmental mechanisms. Trends Neurosci
  38. (1984). Neuropathological findings in primary generalized epilepsy: A study of eight cases. Epilepsia
  39. (2007). Neuropathology of developmental abnormalities.
  40. (2003). Numb and Numblike control cell number during vertebrate neurogenesis. Trends Neurosci
  41. (1988). Proliferation and differentiation of rat neuroepithelial precursor cells in vivo.
  42. (2003). Reelin and disabled-1 expression in developing and mature human cortical neurons.
  43. Schimke immuno-osseous dysplasia: A cell autonomous disorder?Am
  44. Schimke immuno-osseous dysplasia: A clinicopathological correlation.
  45. (1998). Schimke immunoosseous dysplasia complicated by moyamoya phenomenon.
  46. (2007). Schimke immunoosseous dysplasia: Suggestions of genetic diversity. Hum Mutat
  47. (1997). Sequential expression and role of Hu RNAY binding proteins during neurogenesis. Development
  48. (2001). Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development.
  49. (1995). Steroid resistant nephrotic syndrome associated with spondyloepiphyseal dysplasia, transient ischemic attacks and lymphopenia. Clin Nephrol
  50. (2008). Stimulation of oligodendrocyte differentiation in culture by growth in the presence of a monoclonal antibody to sulfated glycolipid.
  51. (2005). The chromatin-remodeling protein ATRX is critical for neuronal survival during corticogenesis.
  52. The development of neural stem cells.
  53. Thickening in the somatosensory cortex of patients with migraine.
  54. (2004). Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration.

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