Whole Transcriptome Analysis (Rna-Seq) By Next-Generation Sequencing of Rubinstein-Taybi syndrome (RSTS) Lymphoblastoid Cell Lines (LCLs)
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PROVIDER: PRJEB75397 | ENA |
REPOSITORIES: ENA
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Project description:Rubinstein-Taybi syndrome (RTS) is a rare and severe genetic developmental disorder characterized by multiple congenital anomalies and intellectual disability. CREBBP and EP300, the two genes known to cause RTS encode transcriptional coactivators with a catalytic lysine acetyltransferase (KAT) activity. Loss of CBP or p300 function results in a deficit in protein acetylation, in particular at histones. In RTS, nothing is known on the consequences of the loss of histone acetylation on the transcriptomic profiles during neuronal differentiation. To address this question, we differentiated induced pluripotent stem cells from RTS patients carrying a recurrent CREBBP mutation that inactivates the KAT domain into cortical and pyramidal neurons. By comparing their acetylome and their transcriptome at different neuronal differentiation timepoints, we identified 25 specific acetylated histone residues altered in RTS. We also identified the transition between neural progenitors and immature neurons as a critical step of the differentiation process, with a delayed neuronal maturation in RTS.
2024-09-09 | GSE239417 | GEO
Project description:Rubinstein-Taybi Syndrome
| PRJEB49962 | ENA
Project description:Rubinstein-Taybi syndrome (RSTS) is a complex autosomal-dominant disease characterized by mental and growth retardation and skeletal abnormalities. A majority of the individuals diagnosed with RSTS carry heterozygous mutation in the gene CREBBP, but a small percentage of cases are caused by mutations in EP300. To investigate the contribution of p300 to RSTS pathoetiology, we carried out a comprehensive and multidisciplinary characterization of p300+/- mice. These mice exhibited facial abnormalities and impaired growth, two traits associated to RSTS in humans. We also observed abnormal gait, reduced swimming speed, enhanced anxiety in the elevated plus maze, and mild cognitive impairment during the transfer task in the water maze. These analyses demonstratethat p300+/- mice exhibit phenotypes that are reminiscent of neurological traits observed in RSTS patients, but their comparison with previous studies on CBP deficient strains also indicate that, in agreement with the most recent findings in human patients, the activity of p300 in cognition is likely less relevant or more susceptible to compensation than the activity of CBP. To identify those genes whose expression was altered in the hippocampus of p300 deficient mutants, we performed a gene profiling analysis of hippocampal tissue using high-density oligonucleotide microarrays. Experiment Overall Design: We obtained triplicate samples containing total RNA from the hippocampi of four 3-month old females of either genotype (in total 12 p300+/- mice and 12 wild type littermates were used in the experiment).
2009-10-10 | E-GEOD-18383 | biostudies-arrayexpress
Project description:Transcriptome and acetylome profiling identify crucial steps of neuronal differentiation in Rubinstein-Taybi syndrome
| PRJNA999240 | ENA
Project description:Expression data from human lymphoblastoid cell lines (LCLs)
| PRJNA793048 | ENA
Project description:Genome-wide DNA methylation patterns are established and maintained by the coordinated action of three DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B. DNMT3B hypomorphic germline mutations are responsible for two-thirds of Immunodeficiency, Centromere Instability, Facial Anomalies (ICF) syndrome cases. The molecular defects in transcription, DNA methylation, and chromatin structure in ICF cells remain relatively uncharacterized. We used expressing microarrays to define the global program of gene expression to elucidate the role of DNMT3B in these processes using EBV-immortalized lymphoblastoid cell lines (LCLs) derived from ICF syndrome and normal individuals. Experiment Overall Design: 5 Normal LCLs (GM08729, GM08728, LCL1, CM304 and CM774) and 3 ICF LCLs (4088,GM08714 and 10759) were selected for RNA extraction and hybridization on Affymetrix UU133A/B microarrays.
2008-06-16 | E-GEOD-9499 | biostudies-arrayexpress
Project description:Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue. Recent studies of the epigenetic mechanisms underlying cognitive functions in mice provide direct evidence for the involvement of nuclear factors (e.g., CBP) in the control of higher cognitive functions. In fact, a role for CBP in higher cognitive function is suggested by the finding that RSTS is caused by heterozygous mutations at the CBP locus (Petrij et al., Nature 376:348-351, 1995). CBP was demonstrated to possess an intrinsic histone acetyltransferase activity (Ogryzko et al., Cell 87:953-959, 1996) that is required for CREB-mediated gene expression (Korzus et al., Science 279:703-707, 1998). The intrinsic protein acetyltransferase activity in CBP might directly destabilize promoter-bound nucleosomes, facilitating the activation of transcription. Due to the complexity of developmental abnormalities and the possible genetic compensation associated with this congenital disorder, however, it is difficult to establish a direct role for CBP in cognitive function in the adult brain. Although aspects of the clinical presentation in RSTS cases have been extensively studied, a spectrum of symptoms found in RSTS patients can be accessed only after birth, and, thus, prenatal genetic tests for this extremely rare genetic disorder are seldom considered. Even though there has been intensive research on the genetic and epigenetic function of the CREBBP gene in rodents, the etiology of this devastating congenital human disorder is largely unknown.
| S-EPMC6863608 | biostudies-literature
Project description:Rubinstein-Taybi syndrome (RSTS; Online Mendelian Inheritance in Man® [OMIM®] #180849, #613684; Orpha: 783 ) is a rare plurimalformative autosomal dominant genetic disorder that affects one in 100,000-125,000 newborns with equal male and female distribution. It is characterized by distinctive facial features, short stature, broad and often angulated thumbs and halluces, and moderate-to-severe intellectual disability. In addition to ocular, cardiac, renal, endocrinologic, neurological, and psychomotor abnormalities, RSTS individuals can present with several gastrointestinal symptoms such as feeding difficulties, gastroesophageal reflux, and constipation. Currently, therapeutic strategies for RSTS involves a multi-disciplinary approach focusing mainly on symptomatic management. Here, we present a case of young-onset Barrett's esophagus in a patient with Rubinstein-Taybi syndrome.
| S-EPMC7769793 | biostudies-literature
Project description:Rubinstein-Taybi syndrome or Broad Thumb-Hallux syndrome is a genetic disorder characterized by facial dysmorphism, growth retardation, and mental deficiency. A seven-year-old girl had come to the Department of Pedodontics, Istanbul Medipol University, Faculty of Dentistry, Turkey, with a complaint of caries and bleeding of gingivae. The patient was mentally retarded. Extraoral features revealed distinctive facial appearance with a broad fore head, hypertelorism, broad nasal bridge, and beaked nose. Intraoral features observed were talons cusps in the upper lateral incisors, carious teeth, and plaque accumulation. Since the patient was mentally retarded, the dental treatment was done under GA. The treatment plan and dental management of this patient are discussed in this case report.
| S-EPMC3443573 | biostudies-literature
Project description:Rubinstein-Taybi syndrome (RTS) is a rare genetic disorder with characteristic physical anomalies. It is characterized by mental retardation, postnatal growth deficiency, microcephaly, specific facial characteristics, broad thumbs, and big toes. Behavioral problems are common with RTS; they include mental retardation, impulsivity, distractibility, instability of mood, stereotypes, poor coordination, atypical depression, and mania. To date, there is lack of literature on the presence of schizophrenia or non-affective psychosis with RTS. Here, we describe two cases where there is co-morbid psychosis with RTS. One case is diagnosed as paranoid schizophrenia and the other as psychosis possibly schizophrenia. Genetic analysis was not done due to unavailability. The possible etiological factors for the association of psychosis with RTS are discussed. Factors such as regulators of RNA polymerase II and hypoxia-inducible factor 1 alpha (HIF1A) may be some common etiological factors for the association of schizophrenia or non-affective psychosis and RTS. Schizophrenia / non-affective psychosis can be a comorbid psychiatric condition with RTS.
| S-EPMC3498786 | biostudies-other