Prenatal presentation of multiple anomalies associated with haploinsufficiency for ARID1A

Slavotinek, Anne; Lefebvre, Mathilde; Bréhin, Anne-Claire; Thauvin, Christel; Patrier, Sophie; Sparks, Teresa N.; Norton, Mary E.; Yu, Jingwei; Huang, Eric J.

doi:10.1016/j.ejmg.2021.104407

Cited by 9 publications

(12 citation statements)

References 31 publications

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“…Slavotinek et al reported that three fetuses presenting with fetal isolated ACC were found to carry ARID1A variants. 11 Hempel et al reported a 5-year-old girl with a neurodevelopmental disorder who had ACC and a SOX11 gene deletion. 12 These results have important implications when ACC is diagnosed prenatally.…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of Coffin‐Siris syndrome: What are the fetal features?

Jing

Lin

et al. 2022

Prenatal Diagnosis

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Objective: To present both our center's and previously reported experience of prenatal diagnosis of Coffin-Siris syndrome (CSS) with regard to the laboratory testing and fetal features of this syndrome. Methods:This was a retrospective study of eight pregnancies with fetal CSS identified by prenatal or postnatal genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray and exome sequencing (ES) results, and pregnancy outcomes.Results: A total of eight cases of fetal CSS based on molecular testing were detected. Two cases presented with an increased nuchal translucency (NT) in the first trimester. The remaining six were identified at the second trimester scan.Agenesis of the corpus callosum (ACC) was the most common sonographic finding, accounting for 5/7 (71.4%) cases in which a second trimester sonogram was performed: four had ACC as an isolated finding, and one had additional features of cerebellar hypoplasia and left congenital diaphragmatic hernia. Conclusion:CSS should be included in the differential diagnosis when ACC is found by prenatal ultrasound. Both chromosomal microarray and ES should be options when counseling patients with a structurally anomalous fetus. Key points What is already known on this topic?� Coffin-Siris syndrome (CSS) is inherited in an autosomal dominant manner; most affected individuals have the disorder as the result of de novo CSS-causing variants of genes in the BAF complex.� In postnatal patients, the diagnosis is based on the presence of major and at least one minor clinical sign. What this study adds?� CSS should be included in the differential diagnosis when a fetus presents with agenesis of the corpus callosum.� In addition to chromosomal microarray, exome sequencing should be an option when counseling patients with a structurally anomalous fetus.Qiu-Xia Yu and Xiang-Yi Jing contributed equally to this study.

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Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of Coffin‐Siris syndrome: What are the fetal features?

Jing

Lin

et al. 2022

Prenatal Diagnosis

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“…CDH is not considered a common finding of CSS based on reviews of large cohorts of individuals with this disorder (Mannino et al, 2018; Vasko et al, 2021), with only two of the 13 patients reviewed here (Subjects 2 and 4) appearing in the Cofin‐Siris Registry maintained by Cofin‐Siris Syndrome Foundation (https://www.coffinsiris.org/). However, an association between CSS and CDH has been suggested based on individual case reports and reviews of CSS and CDH cohorts (Bartin et al, 2018; Delvaux et al, 1998; Knapp et al, 2019; Kosho et al, 2014; Mannino et al, 2018; Scott et al, 2022; Shang et al, 2015; Slavotinek et al, 2022; Sweeney et al, 2018; Tsurusaki et al, 2012; Vasko et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…CDH can be isolated or appear as part of a broader syndrome. Although it is not considered a common feature of CSS, an association between CSS and CDH has been suggested based on case reports and the analysis of CSS and CDH cohorts (Bartin et al, 2018; Delvaux et al, 1998; Knapp et al, 2019; Kosho et al, 2014; Mannino et al, 2018; Scott et al, 2022; Shang et al, 2015; Slavotinek et al, 2022; Sweeney et al, 2018; Tsurusaki et al, 2012; van der Sluijs et al, 2022; Vasko et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Evidence for an association between Coffin‐Siris syndrome and congenital diaphragmatic hernia

Gofin

Zhao

Gerard

et al. 2022

American J of Med Genetics Pt A

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Coffin-Siris syndrome (CSS) is an autosomal dominant neurodevelopmental syndrome that can present with a variety of structural birth defects. Pathogenic variants in 12 genes have been shown to cause CSS. Most of these genes encode proteins that are a part of the mammalian switch/sucrose non-fermentable (mSWI/SNF; BAF) complex. An association between genes that cause CSS and congenital diaphragmatic hernia (CDH) has been suggested based on case reports and the analysis of CSS and CDH cohorts. Here, we describe an unpublished individual with CSS and CDH, and we report additional clinical information on four published cases. Data from these individuals, and a review of the literature, provide evidence that deleterious variants in ARID1B, ARID1A, SMARCB1, SMARCA4, SMARCE1, ARID2, DPF2, and SMARCC2, which are associated with CSS types 1-8, respectively, are associated with the development of CDH. This suggests that additional genetic testing to identify a separate cause of CDH in an individual with CSS may be unwarranted, and that comprehensive genetic testing for individuals with non-isolated CDH should include an evaluation of CSS-related genes. These data also suggest that the mSWI/SNF (BAF) complex may play an important role in diaphragm development.

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“…Human genetic studies have identified dysregulation of ARID1A in Coffin‐Siris syndrome (CSS), a congenital disorder characterized by intellectual disability and growth deficiency. 26 Furthermore, early‐life inflammation and the potential roles for microglia have been documented in immune‐driven animal models of autism and schizophrenia. 27 These studies, together with our previous data showing that Arid1a has a high expression in microglia cells in CNS, 28 suggesting a potential role for Arid1a in microglia and inflammation phenotypes observed in neurodevelopmental disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, Arid1a mutation is correlated with altered expression of various genes and gene sets involved in the immune response, 25 which indicates that Arid1a may have function in immune cells. Human genetic studies have identified dysregulation of ARID1A in Coffin‐Siris syndrome (CSS), a congenital disorder characterized by intellectual disability and growth deficiency 26 . Furthermore, early‐life inflammation and the potential roles for microglia have been documented in immune‐driven animal models of autism and schizophrenia 27 .…”

Section: Introductionmentioning

confidence: 99%

Abnormal microglial polarization induced by Arid1a deletion leads to neuronal differentiation deficits

et al. 2022

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Objective: Microglia, the prototypical innate immune cells of the central nervous system (CNS), are highly plastic and assume their phenotypes dependent on intrinsically genetic, epigenetic regulation or extrinsically microenvironmental cues. Microglia has been recognized as key regulators of neural stem/progenitor cells (NSPCs) and brain functions. Chromatin accessibility is implicated in immune cell development and functional regulation. However, it is still unknown whether and how chromatin remodelling regulates the phenotypic plasticity of microglia and exerts what kind of effects on NSPCs. Methods:We investigated the role of chromatin accessibility in microglia by deleting chromatin remodelling gene Arid1a using microglia-specific Cx3cr1-cre and Cx3cr1-CreERT2 mice. RNA-seq and ATAC-seq were performed to dissect the molecular mechanisms. In addition, we examined postnatal M1/M2 microglia polarization and analysed neuronal differentiation of NSPCs. Finally, we tested the effects of microglial Arid1a deletion on mouse behaviours.Results: Increased chromatin accessibility upon Arid1a ablation resulted in enhanced M1 microglial polarization and weakened M2 polarization, which led to abnormal neurogenesis and anxiety-like behaviours. Switching the polarization state under IL4 stimulation could rescue abnormal neurogenesis, supporting an essential role for chromatin remodeler ARID1A in balancing microglial polarization and brain functions.Conclusions: Our study identifies ARID1A as a central regulator of microglia polarization, establishing a mechanistic link between chromatin remodelling, neurogenesis and mouse behaviours, and highlights the potential development of innovative therapeutics exploiting the innate regenerative capacity of the nervous system. | INTRODUCTIONMicroglia, the only resident immune cells that enduringly reside in the central nervous system (CNS), 1 play vital roles in regulating the homeostasis of CNS. 2 In the past years, studies on microglia have expanded from investigating their immunological functions as resident macrophages of brain and mediators of neuroinflammation, injury, neurodegeneration to understanding their origins and functions involved in complex neurodevelopmental programs in the CNS. [3][4][5][6] Evidence has shown that microglia modulate neurogenesis and synaptic pruning, during which they interact with neural stem/progenitor cells (NSPCs) or neurons to provide trophic support, respond to

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Prenatal presentation of multiple anomalies associated with haploinsufficiency for ARID1A

Cited by 9 publications

References 31 publications

Prenatal diagnosis of Coffin‐Siris syndrome: What are the fetal features?

Prenatal diagnosis of Coffin‐Siris syndrome: What are the fetal features?

Evidence for an association between Coffin‐Siris syndrome and congenital diaphragmatic hernia

Abnormal microglial polarization induced by Arid1a deletion leads to neuronal differentiation deficits

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