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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Different growth patterns in two siblings with Schimke immuno-osseous-dysplasia.
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Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.
Schimke immuno-osseous-dysplasia (SIOD) is an autosomal recessive systemic disease due to pathogenic variants in SMARCAL1. Manifestations include nephrotic syndrome (NS), kidney failure, T-cell dysfunction, vaso-occlusive disease, and disproportionate short stature, a general feature of this disease. Here, we present a markedly different growth pattern in two brothers with SIOD sharing the same homozygous R561C missense variant.
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Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic.
Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment.
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Department of Pediatric Endocrinology, School of Medicine, Marmara University, Istanbul, Türkiye.
Article Synopsis
- * A five-and-a-half-year-old girl with SIOD presented with symptoms like short stature, facial differences, and abnormal blood levels, but initial genetic tests did not identify a pathogenic variant.
- * Further investigation revealed a new genetic mutation associated with SIOD, and this case introduced novel clinical features (hypercalcemia, hypophosphatemia, and elevated FSH) previously unreported in SIOD patients, highlighting the complexity and variability of the disorder.
Loss of helicase C-terminal domain of SMARCAL1 protein associated with severe Schimke immuno-osseous dysplasia.
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Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:
Schimke immuno-osseous dysplasia (SIOD) is a rare multi-system condition caused by biallelic loss-of-function mutations in the SMARCAL1 gene. This disorder is characterized by disproportionate growth failure, T-cell deficiency, and renal dysfunction. Pathogenic variants in the SMARCAL1 gene have been reported in only approximately half of SIOD-affected individuals.
View Article and Find Full Text PDFThe odontoblastic differentiation of dental mesenchymal stem cells: molecular regulation mechanism and related genetic syndromes.
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Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS).
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