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.
Deguchi
Kimiko
K
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
Clewing
Johanna M
JM
Elizondo
Leah I
LI
Hirano
Ryuki
R
Huang
Cheng
C
Choi
Kunho
K
Sloan
Emily A
EA
Lücke
Thomas
T
Marwedel
Katja M
KM
Powell
Ralph D
RD
Santa Cruz
Karen
K
Willaime-Morawek
Sandrine
S
Inoue
Ken
K
Lou
Shu
S
Northrop
Jennifer L
JL
Kanemura
Yonehiro
Y
van der Kooy
Derek
D
Okano
Hideyuki
H
Armstrong
Dawna L
DL
Boerkoel
Cornelius F
CF
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D004265:DNA Helicases / Q000096:biosynthesis*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D051379:Mice; D008831:Microcephaly / Q000209:etiology; D010009:Osteochondrodysplasias / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
C412482:SMARCAL1 protein, human; D004265:DNA Helicases