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Diagnosis is confirmed by genetic testing, usually by non-targeted approaches such as multigene panel or exome sequencing. Differential diagnosis The differential diagnosis includes 22q11.2 deletion syndrome and a number of other neurodevelopmental disorders associated with feeding difficulties, mild developmental delay and variable anomalies.

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage ...

Background Heterozygous mutations in CTCF have been reported in patients with distinct clinical features including intellectual disability. However, the precise pathomechanism underlying the phenotype remains to be uncovered, partly because of the diverse function of CTCF. Here we describe extensive clinical and genetic investigation for two patients with a microdeletion encompassing CTCF .

Mutational spectrum encompasses large deletions, likely gene-disruptive, and missense variants. The identified aberrations in CTCF include two large deletions in 16q22.1, encompassingCTCF plus 26 ...

Taken together, de novo mutations in CTCF in humans cause variable impairment of cognition and growth. Haploinsufficiency is probably the disease mechanism of the phenotypes. Our data suggest that CTCF is required for enhancer-driven gene activation and genomic interaction of enhancers and their regulated gene promoters in development.

Abstract. Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed.

The mechanisms that guide the clonally stable random mono-allelic expression of autosomal genes remain enigmatic. We show that (1) mono-allelically expressed (MAE) genes are assorted and insulated from bi-allelically expressed (BAE) genes through CTCF-mediated chromatin loops; (2) the cell-type-specific dynamics of mono-allelic expression coincides with the gain and loss of chromatin insulator ...

Introduction CTCF -related disorder (CRD) is a neurodevelopmental disorder (NDD) caused by monoallelic pathogenic variants in CTCF . The first CTCF variants in CRD cases were documented in 2013.

Further investigation into the effect of the CTCF R567W mutation on gene expression in E18.5 heart and lung tissues, guided by snRNA-seq and focusing on cardiopulmonary pathological phenotypes in ...

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased applicatio …

Monoallelic variants of CTCF cause an autosomal dominant neurodevelopmental disorder with a wide range of features, including impacts on the brain, growth, and craniofacial development. A growing number of subjects with CTCF-related disorder (CRD) have been identified due to the increased application of exome sequencing, and further delineation of the clinical spectrum of CRD is needed.

Sequence chromatograms showing the novel CTCF frameshift mutation in a heterozygous state in the patient; Panel (a).Both parents were found to harbor wild type CTCF; Panels (b) and (c), in which the AAAG that is deleted by the mutation is highlighted. Discussion and conclusions. The global regulatory role of CTCF in organizing chromatin structure explains the increasing number of studies that ...

Chakraborty et al. studied the role of chromatin structure in the regulation of three FGF genes. Mice with a single CTCF motif deletion in heterozygosity died perinatally with severe phenotypes, showing that even small sequence variants at domain boundaries must be considered as potential sources of gene dysregulation during development and disease.

Introduction: CTCF-related disorder (CRD) is a neurodevelopmental disorder (NDD) caused by monoallelic pathogenic variants in CTCF.The first CTCF variants in CRD cases were documented in 2013. To date, 76 CTCF variants have been further described in the literature. In recent years, due to the increased application of next-generation sequencing (NGS), growing numbers of CTCF variants are being ...

Genetic variants impacting CTCF binding sites associate with several disorders including neurological diseases. The predicted impact of the mutations in ZFs of CTCF on its 3D protein structure and the inferred possible effects on CTCF binding to chromatin. Mutations of CTCF coding sequence in cancer and their functional role in oncogenesis

Monoallelic inactivation of CCCTC-binding factor (CTCF) in human cancer drives altered methylated genomic states, altered CTCF occupancy at promoter and enhancer regions, and deregulated global gene expression. In patients with T cell acute lymphoblastic leukemia (T-ALL), we find that acquired monoa …

Moreover, given the extensive characterization of CTCF as a tumor suppressor gene (120,136,141–143), its frequent mutation in cancer (133,134,136) and loss- or gain-of-function phenotypes , causal links between CTCF-mediated aberrant AS and cancer are likely to emerge (144,145).

Study design. The overall aim of our study was to assess the phenotypic and functional effects of a Finnish founder mutation, 5.2 kb TYROBP deletion, that is known to cause the early-onset neurodegenerative disease NHD in biallelic state. We hypothesized that the monoallelic TYROBP deletion may be a risk factor for neurodegeneration later in life and may induce functional changes in the ...

CCCTC-binding factor CTCF is one of the most important chromatin organizers in vertebrates. It is crucial for orchestrating the three-dimensional chromatin structure by intra- and interchromosomal loop formation and by contributing to the organization of topologically associated domains. 1, 2 Additionally, it is involved in many chromatin regulating processes, including gene regulation ...