Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An adult female with congenital Rubinstein-Taybi syndrome (RTS) and severe mental retardation is described, who presented with symptoms of severe over-activity, short attention span, mood lability, and aggressive outbursts in a cyclical pattern, suggestive of recurrent manic-like episodes. These symptoms improved significantly with divalproex (Depakote) monotherapy. Review of the existing studies showed that 10-76% of persons with RTS may be identified with similar behavioral symptoms. We postulate other persons with RTS may respond to divalproex, and there may be some relationship between the chromosome 16p13.3 deletion and gamma-aminobutyric acid (GABA) receptor or neurotransmitter abnormalities. Recent molecular genetic studies suggest a linkage of this region to bipolar mood disorder and autism, both of which were diagnosed in this patient. Further prospective study is needed of RTS persons regarding behavioral problems, comorbid psychiatric diagnoses, and treatment responses, correlated with genetic abnormalities.
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PMID:Psychopathology, GABA, and the Rubinstein-Taybi syndrome: a review and case study. 1185 81

Research regarding the behavioral aspects of children with Rubinstein-Taybi syndrome (RTS) has suggested some possible behavioral patterns including autistic features. Caregivers of 39 children (mean age = 8.4 years) with RTS (49% showing abnormality in CREBBP gene) and 39 children (mean age = 8.6 years) matched on developmental level, age and gender were administered the Child Behavior Checklist and the Children's Social Behavior Questionnaire. Children with RTS did not exhibit higher internalizing (affective and anxiety symptoms) or externalizing (disruptive symptoms) behavioral problems than expected for their age/developmental range. However, they displayed some specific behaviors: short attention span, motor stereotypies, poor coordination, and overweight. The presence of an identified CREBBP gene abnormality was possibly related to the motor difficulties through impaired motor skills learning.
J Autism Dev Disord 2009 Sep
PMID:Socio-behavioral characteristics of children with Rubinstein-Taybi syndrome. 1935 Mar 77

The array of specialized neuronal and glial cell types that characterize the adult central nervous system originates from neuroepithelial proliferating precursor cells. The transition from proliferating neuroepithelial precursor cells to neuronal lineages is accompanied by rapid global changes in gene expression in coordination with epigenetic modifications at the level of the chromatin structure. A number of genetic studies have begun to reveal how epigenetic deregulation results in neurodevelopmental disorders such as mental retardation, autism, Rubinstein-Taybi syndrome and Rett syndrome. In this review we focus on the role of the methyl-CpG binding protein 2 (MeCP2) during development of the central nervous system and its involvement in Rett syndrome. First, we present recent findings that indicate a previously unconsidered role of glial cells in the development of Rett syndrome. Next, we discuss evidence of how MeCP2 deficiency or loss of function results in aberrant gene expression leading to Rett syndrome. We also discuss MeCP2's function as a repressor and activator of gene expression and the role of its different target genes, including microRNAs, during neuronal development. Finally, we address different signaling pathways that regulate MeCP2 expression at both the post-transcriptional and post-translational level, and discuss how mutations in MeCP2 may result in lack of responsiveness to environmental signals.
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PMID:In sickness and in health: the role of methyl-CpG binding protein 2 in the central nervous system. 2145 47

Syndrome specific repetitive behavior profiles have been described previously. A detailed profile is absent for Rubinstein-Taybi syndrome (RTS). The Repetitive Behaviour Questionnaire and Social Communication Questionnaire were completed for children and adults with RTS (N = 87), Fragile-X (N = 196) and Down (N = 132) syndromes, and individuals reaching cut-off for autism spectrum disorder (N = 228). Total and matched group analyses were conducted. A phenotypic profile of repetitive behavior was found in RTS. The majority of behaviors in RTS were not associated with social-communication deficits or degree of disability. Repetitive behavior should be studied at a fine-grained level. A dissociation of the triad of impairments might be evident in RTS.
J Autism Dev Disord 2015 May
PMID:Repetitive behavior in Rubinstein-Taybi syndrome: parallels with autism spectrum phenomenology. 2549 Oct 25

Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000-720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.
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PMID:Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation. 2576 48

Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant congenital disorder characterized by distinctive facial features, broad thumbs and halluces, growth retardation, and a variable degree of cognitive impairment. CREBBP is the major causative gene and mutations in EP300 are the cause of RTS in a minority of patients. In this study, 17 patients with a clinical diagnosis of RTS were investigated with direct sequencing, MLPA, and array-CGH in search for mutations in these two genes. Eleven patients (64.7%) had disease-causing point mutations or a deletion in CREBBP and in one patient (5.9%) a causal de novo frameshift mutation in EP300 was identified. This patient had broad thumbs, mild intellectual disability, and autism. In addition, an inherited missense mutation of uncertain clinical significance was identified in EP300 in one patient and his healthy father, and three patients had intronic nucleotide changes of uncertain clinical significance in CREBBP. Snoring and sleep apnea were common in both groups and four of the patients' mothers had preeclampsia during pregnancy. Importantly, difficulties associated with anesthesia were frequently reported and included delayed or complicated emergency in 53.3% of patients.
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PMID:CREBBP and EP300 mutational spectrum and clinical presentations in a cohort of Swedish patients with Rubinstein-Taybi syndrome. 2724 63

Working memory (WM) impairments might amplify behavioural difference in genetic syndromes. Murine models of Rubinstein-Taybi syndrome (RTS) evidence memory impairments but there is limited research on memory in RTS. Individuals with RTS and typically developing children completed WM tasks, with participants with RTS completing an IQ assessment and parents/carers completing the Vineland Adaptive Behavior Scales. A cross-sectional trajectory analysis was conducted. There were significant WM span deficits in RTS relative to mental age. Verbal WM span was positively associated with mental age; however, this was not observed for visuo-spatial span. There is a dissociation between WM domains in RTS. Individuals may have difficulties with tasks relying on WM span, above difficulties predicted by overall ability.
J Autism Dev Disord 2016 06
PMID:Dissociation of Cross-Sectional Trajectories for Verbal and Visuo-Spatial Working Memory Development in Rubinstein-Taybi Syndrome. 2701 24

Rubinstein-Taybi syndrome (RTS) is a rare genetic disease that associates intellectual disability with somatic characteristics. We have conducted a study of the overall motor abilities of RTS participants. Static postural performance as well as gait parameters were somewhat decreased, although not significantly compared to typically developing (TD) participants. In contrast, the motor skills requiring a high level of visuomotor coordination were considerably degraded in RTS participants compared to TD participants. We also found that cognitive status was significantly correlated with performance for tasks requiring a higher level of visuomotor coordination in RTS but not TD participants. Our study demonstrates a reduction in the motor performance of RTS participants and a link between the level of intellectual disability and motor capacities.
J Autism Dev Disord 2017 Nov
PMID:Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome. 2874 33

Neurodevelopmental disorders, including intellectual disability and autism spectrum disorder, are often caused by de novo autosomal dominant mutations. While mouse models are frequently used to investigate these disorders, the genetic background sometimes affects the appearance or severity of mutant phenotypes. In a previous report, we developed a system to produce de novo heterozygous mutant mice using the Cre-LoxP system without the need to maintain the heterozygous mutant line itself (Takagi et al. 2015). To further verify the applicability of the de novo mutation system in sperm, we used this system to produce a mouse model for Rubinstein-Taybi syndrome, using a Cbp heterozygous mutant, which has been reported to be difficult to maintain on a C57BL/6 background. Here, we show that de novo Cbp- loss-of-function heterozygous mutant mice with a C57BL/6 background, present with a clear craniofacial phenotype and reduced locomotor activity in the open field test, which was not observed in the loss-of-function of Cbp heterozygous mutant line mice with a mixed genetic background, but was observed in the dominant negative Cbp heterozygous mutant line with a mixed genetic background. Meanwhile, the de novo heterozygous Cbp mutant mice still showed great variability in survival rates despite their inbred background. These results further confirmed that the de novo mutation system used in germ cells is effective for stable production and analysis of an autosomal dominant disorder mouse model, which is often difficult to maintain as a mutant mouse line.
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PMID:Introduction of a de novo Creb-binding protein gene mutation in sperm to produce a Rubinstein-Taybi syndrome model using inbred C57BL/6 mice. 3302 14