Faculty Opinions recommendation of Mutations causing syndromic autism define an axis of synaptic pathophysiology.

AbstractThe aim of this study was to identify the sequence mutations in the Neurexin 1 (NRXN1) gene that has been considered as one of the strong candidate genes. A total of 30 children and adolescents (aged 3-18) with non syndromic autism were enrolled this study. Sequencing of the coding exons and the exon-intron boundaries of the NRXN1 gene was performed. Two known mutations were described in two different cases. Heterozygous S14L was determined in one patient and heterozygous L748I was determined in another patient. The S14L and L748I mutations have been described in the patients with autism before. Both of these mutations were inherited from their father. In this study, two of 30 (6.7%) autism spectrum disorder (ASD) patients carrying NRXN1 gene mutations were detected. It indicates that variants in the NRXN1 gene might confer a risk of developing nonsyndromic ASD. However, due to the reduced penetrance in the gene, the causal role of the NRXN1 gene mutations must be evaluated carefully in all cases.

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Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression

Molecular Autism ◽

10.1186/s13229-016-0082-z ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 19

Author(s):

Emily L. Casanova ◽

Julia L. Sharp ◽

Hrishikesh Chakraborty ◽

Nahid Sultana Sumi ◽

Manuel F. Casanova

Keyword(s):

Gene Expression ◽

Regulate Gene Expression ◽

Syndromic Autism ◽

High Penetrance ◽

Regulate Gene

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Syndromic Autism: Progressing Beyond Current Levels of Description

Review Journal of Autism and Developmental Disorders ◽

10.1007/s40489-017-0116-2 ◽

2017 ◽

Vol 4 (4) ◽

pp. 321-327 ◽

Cited By ~ 9

Author(s):

Jennifer M. Glennon ◽

Annette Karmiloff-Smith ◽

Michael S. C. Thomas

Keyword(s):

Syndromic Autism

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Brief Report: Sensory processing phenotypes in Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability

10.1101/2020.11.30.20241315 ◽

2020 ◽

Author(s):

Ariel M Lyons-Warren ◽

Maria C McCormack ◽

J. Lloyd Holder

Keyword(s):

Intellectual Disability ◽

Sensory Processing ◽

Autism Spectrum ◽

Sensory Profile ◽

Typically Developing ◽

Syndromic Autism ◽

Sensory Features ◽

Syndromic Asd ◽

Underlying Mechanisms ◽

Sensory Profiles

AbstractSensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASD). Significant work has been done to characterize and classify specific sensory profiles in non-syndromic Autism. However, it is not known if syndromic Autism disorders such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID) have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding the underlying mechanisms of the disorders. In this manuscript we use the Short Sensory Profile-2 to characterize sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID and compare their responses to both expected results for typically developing children and published sensory profiles for non-syndromic ASD.

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Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith–Magenis syndrome

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1806796115 ◽

2018 ◽

Vol 115 (42) ◽

pp. 10744-10749 ◽

Cited By ~ 9

Author(s):

Wei-Hsiang Huang ◽

David C. Wang ◽

William E. Allen ◽

Matthew Klope ◽

Hailan Hu ◽

...

Keyword(s):

Social Interaction ◽

Mouse Model ◽

Behavioral Problems ◽

Autism Spectrum ◽

Inhibitory Neurons ◽

Critical Window ◽

Genetic Mouse Model ◽

Expression Of Genes ◽

Syndromic Autism ◽

Level 3

Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith–Magenis syndrome (SMS), a syndromic autism spectrum disorder associated with craniofacial abnormalities, intellectual disability, and behavioral problems. There is currently no cure for SMS. Here, we generated a genetic mouse model to determine the reversibility of SMS-like neurobehavioral phenotypes in Rai1 heterozygous mice. We show that normalizing the Rai1 level 3–4 wk after birth corrected the expression of genes related to neural developmental pathways and fully reversed a social interaction deficit caused by Rai1 haploinsufficiency. In contrast, Rai1 reactivation 7–8 wk after birth was not beneficial. We also demonstrated that the correct Rai1 dose is required in both excitatory and inhibitory neurons for proper social interactions. Finally, we found that Rai1 heterozygous mice exhibited a reduction of dendritic spines in the medial prefrontal cortex (mPFC) and that optogenetic activation of mPFC neurons in adults improved the social interaction deficit of Rai1 heterozygous mice. Together, these results suggest the existence of a postnatal temporal window during which restoring Rai1 can improve the transcriptional and social behavioral deficits in a mouse model of SMS. It is possible that circuit-level interventions would be beneficial beyond this critical window.

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Investigation the etiology of syndromic autism with targeted gene analysis

Annals of Medical Research ◽

10.5455/annalsmedres.2021.03.240 ◽

2021 ◽

Vol 28 (12) ◽

pp. 2174

Author(s):

Sinem Yalcintepe ◽

Hakan Gurkan ◽

Selma Demir ◽

Leyla Bozatli ◽

Engin Atli ◽

...

Keyword(s):

Gene Analysis ◽

Syndromic Autism

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Tsc2Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

Autism Research and Treatment ◽

10.1155/2014/761279 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Dan Ehninger

Keyword(s):

Immune Activation ◽

Viral Infections ◽

Genetic Disorder ◽

Fetal Brain ◽

Mtor Signaling ◽

Interactive Effects ◽

Poly I:C ◽

Cellular Processes ◽

Syndromic Autism ◽

Cytokine Levels

Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygousTSC1orTSC2mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygousTsc2mutation and the poly I:C model of maternal immune activation (MIA) interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater inTsc2+/−than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect ofTsc2haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable inTsc2haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects ofTsc2haploinsufficiency and MIA.

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