scholarly journals Absence of Substantial Copy Number Differences in a Pair of Monozygotic Twins Discordant for Features of Autism Spectrum Disorder

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Marina Laplana ◽  
José Luis Royo ◽  
Anton Aluja ◽  
Ricard López ◽  
Damiàn Heine-Sunyer ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Communication Skills ◽  
Copy Number ◽  
De Novo ◽  
Significant Proportion ◽  
Clinical Manifestations ◽  
Monozygotic Twins ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Comparative Genome Hybridization

Autism spectrum disorder (ASD) is a highly heritable disease (~0.9) with a complex genetic etiology. It is initially characterized by altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in social interaction. Despite the large amount of studies described so far, the high clinical diversity affecting the autism phenotype remains poorly explained. Recent studies suggest that rare genomic variations, in particular copy number variation (CNV), may account for a significant proportion of the genetic basis of ASD. The use of disease-discordant monozygotic twins represents a powerful strategy to identifyde novoand inherited CNV in the disorder. Here we present the results of a comparative genome hybridization (CGH) analysis with a pair of monozygotic twins affected of ASD with significant differences in their clinical manifestations that specially affect speech language impairment and communication skills. Array CGH was performed in three different tissues: blood, saliva, and hair follicle, in an attempt to identify germinal and somatic CNV regions that may explain these differences. Our results argue against a role of large CNV rearrangements as a molecular etiology of the observed differences. This forwards future research to explorede novopoint mutation and epigenomic alterations as potential explanations of the observed clinical differences.

scholarly journals A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Livia O. Loureiro ◽  
Jennifer L. Howe ◽  
Miriam S. Reuter ◽  
Alana Iaboni ◽  
Kristina Calli ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Copy Number ◽  
De Novo ◽  
Sequence Data ◽  
Copy Number Variants ◽  
Somatic Mosaicism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Variable Expression ◽  
Genomic Location

AbstractAutism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome sequence data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 18 individuals from 16 unrelated families carrying a heterozygous guanine duplication (c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (genomic location [hg38]g.50,721,512dup) affecting SHANK3, a prototypical ASD gene (0.08% of ASD-affected individuals carried the predicted p.Ala1227Glyfs*69 frameshift variant). Most probands carried de novo mutations, but five individuals in three families inherited it through somatic mosaicism. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (17/17) formally tested for ASD carried a diagnosis, there was the variable expression of core ASD features both within and between families. Defining such recurrent mutational mechanisms underlying an ASD outcome is important for genetic counseling and early intervention.

scholarly journals Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mouse Model ◽  
Mouse Models ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

scholarly journals Natural language processing (NLP) tools in extracting biomedical concepts from research articles: a case study on autism spectrum disorder

2020 ◽  
Vol 20 (S11) ◽  
Author(s):  
Jacqueline Peng ◽  
Mengge Zhao ◽  
James Havrilla ◽  
Cong Liu ◽  
Chunhua Weng ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Natural Language Processing ◽  
Natural Language ◽  
Language Processing ◽  
Clinical Manifestations ◽  
Predictive Performance ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Research Articles

Abstract Background Natural language processing (NLP) tools can facilitate the extraction of biomedical concepts from unstructured free texts, such as research articles or clinical notes. The NLP software tools CLAMP, cTAKES, and MetaMap are among the most widely used tools to extract biomedical concept entities. However, their performance in extracting disease-specific terminology from literature has not been compared extensively, especially for complex neuropsychiatric disorders with a diverse set of phenotypic and clinical manifestations. Methods We comparatively evaluated these NLP tools using autism spectrum disorder (ASD) as a case study. We collected 827 ASD-related terms based on previous literature as the benchmark list for performance evaluation. Then, we applied CLAMP, cTAKES, and MetaMap on 544 full-text articles and 20,408 abstracts from PubMed to extract ASD-related terms. We evaluated the predictive performance using precision, recall, and F1 score. Results We found that CLAMP has the best performance in terms of F1 score followed by cTAKES and then MetaMap. Our results show that CLAMP has much higher precision than cTAKES and MetaMap, while cTAKES and MetaMap have higher recall than CLAMP. Conclusion The analysis protocols used in this study can be applied to other neuropsychiatric or neurodevelopmental disorders that lack well-defined terminology sets to describe their phenotypic presentations.

scholarly journals Rare Copy Number Variations in a Chinese Cohort of Autism Spectrum Disorder

2018 ◽  
Vol 9 ◽  
Author(s):  
Yanjie Fan ◽  
Xiujuan Du ◽  
Xin Liu ◽  
Lili Wang ◽  
Fei Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Copy Number ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Spectrum Disorder ◽  
Chinese Cohort

scholarly journals Caregiver-mediated approaches to managing challenging behaviors in children with autism spectrum disorder

2013 ◽  
Vol 15 (2) ◽  
pp. 225-233
Keyword(s):  
Autism Spectrum Disorder ◽  
Children And Adolescents ◽  
Behavioral Interventions ◽  
Challenging Behaviors ◽  
Significant Proportion ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Children With Asd ◽  
Adolescents With Asd

A significant proportion of children with autism spectrum disorder (ASD) are referred to mental health centers due to the presence of challenging behaviors. Because challenging behaviors in children and adolescents with ASD often result from underlying social and communication difficulties and comorbid anxiety, traditional caregiver-mediated behavior intervention techniques developed for children with disruptive behavior disorders may need to be adapted for this population. Behavioral interventions that target communication skills, social skills, anxiety, and sensory responsiveness in children with ASD may be needed. Notably, while best practice necessitates the involvement of caregivers in treating children and adolescents with ASD, few randomized control studies have examined the effectiveness of caregiver-implemented interventions in reducing challenging behaviors. This review summarizes the current literature with regard to caregiver-mediated behavioral interventions for children with ASD, and suggests areas for intervention development and research.

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