<i>SATB2</i>‐associated syndrome: Mechanisms, phenotype, and practical recommendations

Zárate, Yuri A.; Fish, Jennifer L.

doi:10.1002/ajmg.a.38022

Cited by 90 publications

(134 citation statements)

References 47 publications

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“…When looking at these 3 variable phenotypic features by the underlying type of pathogenic variant (nonsense, frameshift, missense, or splice site), cleft palate was more prevalent in individuals with frameshift (63%) or nonsense (67%) pathogenic variants compared to missense (17%) alterations but this difference was not statistically significant ( P = .0544). For comparison, in 17 individuals with large deletions that include SATB2 , tibial bowing has not been reported (but seen in 1/3 individuals with intragenic duplications) while cleft palate has been described in 47% (8/17) …”

Section: Resultsmentioning

confidence: 97%

“…From the neurodevelopmental perspective, developmental delay (DD)/intellectual disability (ID) with absent or limited speech development is virtually universal . A total of 42 individuals with SAS have been described thus far . Alterations in the SATB2 gene can result from a variety of different mechanisms that include contiguous deletions, intragenic deletions and duplications, translocations with secondary gene disruption, and point pathogenic variants .…”

Section: Introductionmentioning

confidence: 95%

“…SATB2 ‐associated syndrome (SAS; OMIM 612313) is a clinically recognizable syndrome characterized by neurodevelopmental and behavioral abnormalities, palatal and dental anomalies, dysmorphic features, and frequent skeletal pathology . From the neurodevelopmental perspective, developmental delay (DD)/intellectual disability (ID) with absent or limited speech development is virtually universal . A total of 42 individuals with SAS have been described thus far .…”

Section: Introductionmentioning

confidence: 99%

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Genotype and phenotype in 12 additional individuals with SATB2‐associated syndrome

et al. 2017

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SATB2-associated syndrome (SAS) is a multisystemic disorder caused by alterations of the SATB2 gene. We describe the phenotype and genotype of 12 individuals with 10 unique (de novo in 11 of 11 tested) pathogenic variants (1 splice site, 5 frameshift, 3 nonsense, and 2 missense) in SATB2 and review all cases reported in the published literature caused by point alterations thus far. In the cohort here described, developmental delay (DD) with severe speech compromise, facial dysmorphism, and dental anomalies were present in all cases. We also present the third case of tibial bowing in an individual who, just as in the previous 2 individuals in the literature, also had a truncating pathogenic variant of SATB2. We explore early genotype-phenotype correlations and reaffirm the main clinical features of this recognizable syndrome: universal DD with severe speech impediment, mild facial dysmorphism, and high frequency of craniofacial anomalies, behavioral issues, and brain neuroradiographic changes. As the recently proposed surveillance guidelines for individuals with SAS are adopted by providers, further delineation of the frequency and impact of other phenotypic traits will become available. Similarly, as new cases of SAS are identified, further exploration of genotype-phenotype correlations will be possible.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Genotype and phenotype in 12 additional individuals with SATB2‐associated syndrome

et al. 2017

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“…Moreover, patients with mutations or deletions within the SATB2 locus, a condition referred to as ‘SATB2-associated syndrome (SAS)’, exhibit severe learning difficulties and profound mental retardation, providing further indication for a potential role of SATB2 in higher brain function (Liedén et al, 2014; Zarate et al, 2015; Zarate and Fish, 2016; Marshall et al, 2008). So far the neuropsychiatric symptoms of SAS have been discussed in the context of the established role of Satb2 during embryonic development of the cerebral cortex.…”

Section: Introductionmentioning

confidence: 99%

Satb2 determines miRNA expression and long-term memory in the adult central nervous system

Jaitner

Reddy

Abentung

et al. 2016

eLife

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SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.DOI: http://dx.doi.org/10.7554/eLife.17361.001

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“…SATB2 resides in the gene poor region, 2q32‐q33, and was first isolated from human fetal brain cDNA library as a part of the Human Unidentified Gene‐Encoded (HUGE) protein database project . SATB2 is a transcription factor critically important for the biological development of various tissues such as osteoblast, as well as differentiation of neurons, and stem cells . In addition, SATB2 is also considered a nuclear matrix attachment region (MAR) binding protein .…”

Section: Introductionmentioning

confidence: 99%

Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation

Chen

Sun

et al. 2018

Molecular Carcinogenesis

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Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic-contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic-induced carcinogenesis. Arsenic down-regulated miRNA-31 and the release of this inhibition caused overexpression of special AT-rich sequence-binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR-31 expression. As a direct downstream target of miR-31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR-31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS-2B) cells indicating the importance of the expression of miR-31 in preventing carcinogenesis by suppressing SATB2 protein levels.

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SATB2‐associated syndrome: Mechanisms, phenotype, and practical recommendations

Cited by 90 publications

References 47 publications

Genotype and phenotype in 12 additional individuals with SATB2‐associated syndrome

Genotype and phenotype in 12 additional individuals with SATB2‐associated syndrome

Satb2 determines miRNA expression and long-term memory in the adult central nervous system

Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation

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