Further supporting evidence for the <i>SATB2</i>‐associated syndrome found through whole exome sequencing

Zárate, Yuri A.; Perry, Hazel; Ben‐Omran, Tawfeg; Sellars, Elizabeth A.; Stein, Quinn; Al‐Mureikhi, Mariam; Simmons, Katharine B.; Klein, Ophir D.; Fish, Jennifer L.; Feingold, Murray; Douglas, Jessica; Kruer, Michael C.; Si, Yue; Mao, Rong; McKnight, Dianalee; Gibellini, Federica; Retterer, Kyle; Slavotinek, Anne

doi:10.1002/ajmg.a.36849

Cited by 45 publications

(64 citation statements)

References 21 publications

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“…Clinical phenotypes associated with SATB2 or EHMT1 mutations have implicated several organs beyond brain, notably palate, bone and brachial arch derivatives in SATB2 mutation cases (Zarate et al 2015), and cardiac anomalies in EHMT1 mutation cases (Kleefstra et al 2006;Tachibana et al 2005). To determine if expression of these genes is higher in organs known to be associated with disease in adult tissues, we took advantage of RNA sequencing data from GTEx (Mele et al 2015) (Supplementary Fig.…”

Section: Satb2 Tcf7l2 and Ehmt1 Are Expressed In Proliferating And mentioning

confidence: 99%

Investigation of genes important in neurodevelopment disorders in adult human brain

et al. 2015

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Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

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Section: Satb2 Tcf7l2 and Ehmt1 Are Expressed In Proliferating And mentioning

confidence: 99%

Investigation of genes important in neurodevelopment disorders in adult human brain

et al. 2015

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“…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 .…”

Section: Introductionmentioning

confidence: 99%

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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“…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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Further supporting evidence for the SATB2‐associated syndrome found through whole exome sequencing

Cited by 45 publications

References 21 publications

Investigation of genes important in neurodevelopment disorders in adult human brain

Investigation of genes important in neurodevelopment disorders in adult human brain

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

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