TY - JOUR
T1 - Neurologic phenotype of schimke immuno-osseous dysplasia and neurodevelopmental expression of SMARCAL1
AU - Deguchi, Kimiko
AU - Clewing, Johanna Marietta
AU - Elizondo, Leah I.
AU - Hirano, Ryuki
AU - Huang, Cheng
AU - Choi, Kunho
AU - Sloan, Emily A.
AU - Lücke, Thomas
AU - Marwedel, Katja M.
AU - Powell, Ralph D.
AU - Santa Cruz, Karen
AU - Willaime-Morawek, Sandrine
AU - Inoue, Ken
AU - Lou, Shu
AU - Northrop, Jennifer L.
AU - Kanemura, Yonehiro
AU - Van Der Kooy, Derek
AU - Okano, Hideyuki
AU - Armstrong, Dawna L.
AU - Boerkoel, Cornelius F.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Immunodeficiency
KW - Microcephaly
KW - Neural stem cell
KW - Neuronal migration
KW - Renal disease
KW - Skeletal dysplasia
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U2 - 10.1097/NEN.0b013e3181772777
DO - 10.1097/NEN.0b013e3181772777
M3 - Article
C2 - 18520775
AN - SCOPUS:44649161316
SN - 0022-3069
VL - 67
SP - 565
EP - 577
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 6
ER -