Chd2

Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or without absence seizures, 2. eye closure induced seizures or EEG paroxysms, 3. clinical or EEG photosensitivity. While eyelid myoclonia is the disease hallmark, other seizure types, including absence seizures and generalized tonic-clonic seizures, may be present. It is thought to have a genetic etiology, and around one-third of patients may have a positive family history of epilepsy...

The development regulation of the uterine-vaginal junction (UVJ) epithelial folds during the sexual maturation of female birds played crucial roles in the adults' sperm storage duration and fertilization capability. However, there is a lack of studies on it in the breeding field of laying hens. In this study, White Leghorn was used for the morphological and developmental studies. According to the morphological characteristics, the development of the UVJ epithelial folds was classified into 4 stages (morphological stage T1-T4)...

BACKGROUND AND OBJECTIVES: The genetic developmental and epileptic encephalopathies (DEEs) comprise a large group of severe epilepsy syndromes, with a wide phenotypic spectrum. Currently, the rates of convulsive status epilepticus (CSE), nonconvulsive status epilepticus (NCSE), and sudden unexplained death in epilepsy (SUDEP) in these diseases are not well understood. We aimed to describe the proportions of patients with frequently observed genetic DEEs who developed CSE, NCSE, mortality, and SUDEP...

Childhood-onset schizophrenia (COS) is a rare form of schizophrenia with an onset prior to 13 years of age. Although genetic factors play a role in COS etiology, only a few causal variants have been reported to date. This study presents a diagnostic exome sequencing (ES) in 37 Israeli Jewish families with a proband diagnosed with COS. By implementing a trio/duo ES approach and applying a well-established diagnostic pipeline, we detected clinically significant variants in 7 probands (19 %). These single nucleotide variants and indels were mostly inherited...

UNLABELLED: Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing of recurrent CLL loss-of-function drivers in mice and recapitulated the process of transformation from indolent CLL into large cell lymphoma [i.e., Richter syndrome (RS)]. Evolutionary trajectories of 64 mice carrying diverse combinatorial gene assortments revealed coselection of mutations in Trp53, Mga, and Chd2 and the dual impact of clonal Mga/Chd2 mutations on E2F/MYC and interferon signaling dysregulation...

Chromodomain helicase DNA-binding domain 2 (CHD2) is a chromatin remodeling factor involved in many developmental processes. However, its role in male germ cell development has not been elucidated. Here, we confirm that CHD2 expression is enriched in the male germline. In a heterozygous knockout mouse model of Chd2 ( Chd2 +/- ), we demonstrated that Chd2 haploinsufficiency resulted in testicular developmental delay, an increased rate of abnormal sperm, and impaired fertility in mice. In vitro experiments in mouse spermatogonia showed that CHD2 knockdown inhibits spermatogonial self-renewal...

Xq25 microduplication involving exclusively STAG2 is a new distinctive cohesinopathy including mild to moderate intellectual disability, speech delay and facial dysmorphism. Seizures seem to be scarce, but detailed seizure type descriptions are missing. We report the case of an 8-year-old boy with mild intellectual disability and eyelid myoclonia with onset at age of 3 years, initially misinterpreted as tics. An ictal VIDEO-EEG documented eye closure elicited generalized 3 Hz spike-waves or polyspike-waves concomitant to eyelid myoclonia, sometimes associated to brief clinically observable absences...

Vagus nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy (DRE). The present study evaluated the efficacy of VNS in pediatric patients with DRE of monogenic etiology. A total of 20 patients who received VNS treatment at our center were followed up every 3 months through outpatient visits or a remote programming platform. The median follow-up time was 1.4 years (range: 1.0-2.9). The rate of response to VNS at 12 months of follow-up was 55.0% (11/20) and the seizure-free rate was 10...

Mutations in the chromodomain helicase DNA binding protein 2 (CHD2) gene are associated with neurodevelopmental disorders. However, mechanisms by which CHD2 regulates human brain development remain largely uncharacterized. Here, we used a human embryonic stem cell model of cortical interneuron (hcIN) development to elucidate its roles in this process. We identified genome-wide CHD2 binding profiles during hcIN differentiation, defining direct CHD2 targets related to neurogenesis in hcIN progenitors and to neuronal function in hcINs...

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation, variable severity, and multiple comorbidities. A complex underlying genetic architecture matches the clinical heterogeneity, and evidence indicates that several co-occurring brain disorders share a genetic component with ASD. In this study, we established a genetic similarity disease network approach to explore the shared genetics between ASD and frequent comorbid brain diseases (and subtypes), namely Intellectual Disability, Attention-Deficit/Hyperactivity Disorder, and Epilepsy, as well as other rarely co-occurring neuropsychiatric conditions in the Schizophrenia and Bipolar Disease spectrum...

Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration's (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments...

Objective: To determine the contribution of genetic etiologies in epilepsy with photosensitivity. Methods: A total of 35 epileptic patients with genetic photosensitivity from January 2019 to May 2021 were analyzed. Results: Pathogenic variants were identified in 35 patients, including SCN1A (7) CHD2 (6), TPP1 (3), SYNGAP1 (3), GABRA1 (2), GABRG2 (1), KCTD7 (1), MFSD8 (1), KCNC1 (1) GBA (1), CACNA1A (1), KCNMA1 (1), FLNA (1), SZT2 (1), SLC2A1 (1), 5q33...

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide that endangers human health. Transcription factors (TFs) have gradually become hot spots for drug development in NAFLD for their impacts on metabolism. However, the specific TFs that regulate immune response in the development of NAFLD is not clear. This study aimed to investigate the TFs involved in the immune response of NAFLD and provide novel targets for drug development. Methods: Microarray data were obtained from liver samples from 26 normal volunteers and 109 NAFLD patients using the Gene Expression Omnibus (GEO) database...

PURPOSE OF REVIEW: ATP-dependent chromatin remodeling factors utilize energy from ATP hydrolysis to modulate DNA-histone structures and regulate gene transcription. They are essential during hematopoiesis and for hematopoietic stem and progenitor cell (HSPC) function. This review discusses the recently unveiled roles of these chromatin remodelers in HSPC regulation, with an emphasis on the mechanism of chromodomain helicase DNA-binding (CHD) family members. RECENT FINDINGS: Recent studies of ATP-dependent chromatin remodelers have revealed that individual CHD family members engage in distinct mechanisms in regulating HSPC cell fate...

Importance: CHD2 is a member of the chromodomain helicase DNA-binding (CHD) family of proteins, which have important roles in the regulation of gene expression. Dysregulation of this protein may lead to various disorders. Objective: To delineate the genotypes and phenotypes of CHD2-related epilepsy. Methods: We analyzed the medical history, magnetic resonance imaging findings, and video-electroencephalogram recordings of 17 patients with CHD2 mutations in the Neurology Department of Beijing Children's Hospital from June 2016 to June 2021...

No abstract text is available yet for this article.

Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic CHD2 variants. While only a few pathogenic CHD2 variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic CHD2 variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients...

Background: The chromodomain helicase DNA-binding protein 2 ( CHD2 ) gene, is an ATPase and part of the CHD family of chromatin remodelers. Mutations in the CHD2 gene are inherited in an autosomal-dominant manner and can lead to intellectual disability, epilepsy, and autism. We investigated the clinical characteristics of CHD2 -related conditions and their possible pathogenesis. Methods: We collected and analysed the clinical data of patients that were identified as having CHD2 mutations. Genetic testing was performed using targeted sequencing or whole-exome sequencing...

Background: Dravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene SCN1A , which encodes the voltage-gated sodium channel NaV 1. 1 in the brain. While SCN1A mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to SCN1A ...

BACKGROUND: Sporadic nonlesional intractable visual-sensitive epilepsies of childhood represent a challenging subset of epilepsies in terms of management and prognostication given a propensity to evolve as epileptic encephalopathy. OBJECTIVE: To study the genetic heterogeneity of drug-resistant visual sensitive epilepsy of childhood. METHODS: A retrospective chart review was conducted on patients in the pediatric age group between 2016 and 2018, with drug-resistant epilepsy (DRE) and video electro encephalography (VEEG) documented reflex photosensitivity, eye-condition sensitivity...