scholarly journals Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder

2009 ◽  
Vol 47 (3) ◽  
pp. 195-203 ◽  
Author(s):  
B. A. Fernandez ◽  
W. Roberts ◽  
B. Chung ◽  
R. Weksberg ◽  
S. Meyn ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Phenotypic Spectrum

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.

A de novo mosaic mutation in SPAST with two novel alternative alleles and chromosomal copy number variant in a boy with spastic paraplegia and autism spectrum disorder

2017 ◽  
Vol 60 (10) ◽  
pp. 548-552 ◽  
Author(s):  
A.M. Matthews ◽  
M. Tarailo-Graovac ◽  
E.M. Price ◽  
I. Blydt-Hansen ◽  
A. Ghani ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Copy Number ◽  
De Novo ◽  
Copy Number Variant ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Spastic Paraplegia ◽  
Chromosomal Copy Number ◽  
Chromosomal Copy

scholarly journals Increased burden of deleterious variants in essential genes in autism spectrum disorder

2016 ◽  
Vol 113 (52) ◽  
pp. 15054-15059 ◽  
Author(s):  
Xiao Ji ◽  
Rachel L. Kember ◽  
Christopher D. Brown ◽  
Maja Bućan
Keyword(s):  
Autism Spectrum Disorder ◽  
Large Scale ◽  
De Novo ◽  
Autism Spectrum ◽  
Essential Genes ◽  
Spectrum Disorder ◽  
Model Organisms ◽  
Disease Genes ◽  
Priority List ◽  
Human Orthologs

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.

scholarly journals De novo Mutations (DNMs) in Autism Spectrum Disorder (ASD): Pathway and Network Analysis

2018 ◽  
Vol 9 ◽  
Author(s):  
Aitana Alonso-Gonzalez ◽  
Cristina Rodriguez-Fontenla ◽  
Angel Carracedo
Keyword(s):  
Autism Spectrum Disorder ◽  
Network Analysis ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutations

scholarly journals De novo genic mutations among a Chinese autism spectrum disorder cohort

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Tianyun Wang ◽  
Hui Guo ◽  
Bo Xiong ◽  
Holly A.F. Stessman ◽  
Huidan Wu ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability

2015 ◽  
Vol 24 (6) ◽  
pp. 838-843 ◽  
Author(s):  
Anne-Laure Mosca-Boidron ◽  
Lucie Gueneau ◽  
Guillaume Huguet ◽  
Alice Goldenberg ◽  
Céline Henry ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Intellectual Disability ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder

Rare de novo deletion of metabotropic glutamate receptor 7 (GRM7) gene in a patient with autism spectrum disorder

2015 ◽  
Vol 168 (4) ◽  
pp. 258-264 ◽  
Author(s):  
Yi Liu ◽  
Yanqing Zhang ◽  
Dongmei Zhao ◽  
Rui Dong ◽  
Xiaomeng Yang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Metabotropic Glutamate

scholarly journals Autism spectrum disorder severity reflects the average contribution of de novo and familial influences

2014 ◽  
Vol 111 (42) ◽  
pp. 15161-15165 ◽  
Author(s):  
Elise B. Robinson ◽  
Kaitlin E. Samocha ◽  
Jack A. Kosmicki ◽  
Lauren McGrath ◽  
Benjamin M. Neale ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Familial Influences ◽  
Average Contribution

scholarly journals An autism spectrum disorder-related de novo mutation hotspot discovered in the GEF1 domain of Trio

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Anastasiia Sadybekov ◽  
Chen Tian ◽  
Cosimo Arnesano ◽  
Vsevolod Katritch ◽  
Bruce E. Herring
Keyword(s):  
Autism Spectrum Disorder ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation
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