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

Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1
Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1
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.
immunodeficiency, microcephaly, neural stem cell, neuronal migration, renal disease, skeletal dysplasia
0022-3069
565-577
Deguchi, K.
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Clewing, J.M.
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Elizondo, L.I.
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Hirano, R.
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Huang, C.
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Choi, K.
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Sloan, E.A.
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Lucke, T.
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Marwedel, K.M.
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Powell, R.
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SantaCruz, K.
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Fujita, Y.
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Willaime-Morawek, S.
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Inoue, K.
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Lou, S.
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Northrop, J.
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Kanemura, Y.
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van der Kooy, D.
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Okano, H.
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Armstrong, D.L.
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Boerkoel, C.F.
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Deguchi, K.
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Clewing, J.M.
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Elizondo, L.I.
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Hirano, R.
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Huang, C.
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Choi, K.
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Sloan, E.A.
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Lucke, T.
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Marwedel, K.M.
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Powell, R.
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SantaCruz, K.
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Fujita, Y.
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Willaime-Morawek, S.
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Inoue, K.
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Lou, S.
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Northrop, J.
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Kanemura, Y.
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van der Kooy, D.
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Okano, H.
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Armstrong, D.L.
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Boerkoel, C.F.
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Deguchi, K., Clewing, J.M., Elizondo, L.I., Hirano, R., Huang, C., Choi, K., Sloan, E.A., Lucke, T., Marwedel, K.M., Powell, R., SantaCruz, K., Fujita, Y., Willaime-Morawek, S., Inoue, K., Lou, S., Northrop, J., Kanemura, Y., van der Kooy, D., Okano, H., Armstrong, D.L. and Boerkoel, C.F. (2008) Neurologic phenotype of Schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1. Journal of Neuropathology and Experimental Neurology, 67 (6), 565-577. (doi:10.1097/NEN.0b013e3181772777). (PMID:18520775)

Record type: Article

Abstract

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.

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Published date: June 2008
Keywords: immunodeficiency, microcephaly, neural stem cell, neuronal migration, renal disease, skeletal dysplasia
Organisations: Clinical Neurosciences

Identifiers

Local EPrints ID: 66444
URI: http://eprints.soton.ac.uk/id/eprint/66444
ISSN: 0022-3069
PURE UUID: 862fe7e7-134d-4c0a-94b9-7b18148e2c3e
ORCID for S. Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

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Date deposited: 15 Jun 2009
Last modified: 14 Mar 2024 02:53

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Contributors

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

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