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.
Department of Pathology, Baylor College of Medicine, Houston, Texas, USA.
Kimiko
K
Deguchi
Johanna M
JM
Clewing
Leah I
LI
Elizondo
Ryuki
R
Hirano
Cheng
C
Huang
Kunho
K
Choi
Emily A
EA
Sloan
Thomas
T
Lücke
Katja M
KM
Marwedel
Ralph D
RD
Powell
Karen
K
Santa Cruz
Sandrine
S
Willaime-Morawek
Ken
K
Inoue
Shu
S
Lou
Jennifer L
JL
Northrop
Yonehiro
Y
Kanemura
Derek
D
van der Kooy
Hideyuki
H
Okano
Dawna L
DL
Armstrong
Cornelius F
CF
Boerkoel
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