Syndromic Autism Revisited: Review of the Literature and Lessons Learned

Ziats, Catherine A.; Patterson, Wesley G.; Friez, Michael J.

doi:10.1016/j.pediatrneurol.2020.06.011

Cited by 36 publications

(24 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To date, more than 50 deletion and duplication syndromes associated with an autism phenotype have been described and sex chromosomal aneuploidies have the highest association with autism [ 37 ]. Genetic abnormalities of the chromosome 15q11-q13 region are an important cause for ASD, which account for approximately 1% of cases [ 38 ].…”

Section: Genetics Studiesmentioning

confidence: 99%

Molecular Dysregulation in Autism Spectrum Disorder

Gill

Clothier

Veerapandiyan

et al. 2021

JPM

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) comprises a heterogeneous group of neurodevelopmental disorders with a strong heritable genetic component. At present, ASD is diagnosed solely by behavioral criteria. Advances in genomic analysis have contributed to numerous candidate genes for the risk of ASD, where rare mutations and s common variants contribute to its susceptibility. Moreover, studies show rare de novo variants, copy number variation and single nucleotide polymorphisms (SNPs) also impact neurodevelopment signaling. Exploration of rare and common variants involved in common dysregulated pathways can provide new diagnostic and therapeutic strategies for ASD. Contributions of current innovative molecular strategies to understand etiology of ASD will be explored which are focused on whole exome sequencing (WES), whole genome sequencing (WGS), microRNA, long non-coding RNAs and CRISPR/Cas9 models. Some promising areas of pharmacogenomic and endophenotype directed therapies as novel personalized treatment and prevention will be discussed.

show abstract

Section: Genetics Studiesmentioning

confidence: 99%

Molecular Dysregulation in Autism Spectrum Disorder

Gill

Clothier

Veerapandiyan

et al. 2021

JPM

View full text Add to dashboard Cite

show abstract

“…Our monogenetic subgroup of ASD children with SHANK3 defects exhibited both common and distinct disruptions in local and networked structural organization compared to those idiopathic ASD, suggesting both common and distinct neuropathological mechanisms underlying ASD with and without SHANK3 deficiency. Differentiating the heterogeneity in ASD is critical to both clinicians and researchers to understand the phenotype and pathophysiology of the syndrome (Agelink van Rentergem et al, 2021;Ziats et al, 2021). Our study of monogenic ASD patients may thus offer new insights into the diverse findings of previous neuroimaging studies of idiopathic ASD.…”

Section: Discussionmentioning

confidence: 98%

Common and Distinct Disruptions of Cortical Surface Morphology Between Autism Spectrum Disorder Children With and Without SHANK3 Deficiency

Liu

Huang

et al. 2021

Front. Neurosci.

View full text Add to dashboard Cite

SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3)-caused autism spectrum disorder (ASD) may present a unique opportunity to clarify the heterogeneous neuropathological mechanisms of ASD. However, the specificity and commonality of disrupted large-scale brain organization in SHANK3-deficient children remain largely unknown. The present study combined genetic tests, neurobehavioral evaluations, and magnetic resonance imaging, aiming to explore the disruptions of both local and networked cortical structural organization in ASD children with and without SHANK3 deficiency. Multiple surface morphological parameters such as cortical thickness (CT) and sulcus depth were estimated, and the graph theory was adopted to characterize the topological properties of structural covariance networks (SCNs). Finally, a correlation analysis between the alterations in brain morphological features and the neurobehavioral evaluations was performed. Compared with typically developed children, increased CT and reduced nodal degree were found in both ASD children with and without SHANK3 defects mainly in the lateral temporal cortex, prefrontal cortex (PFC), temporo-parietal junction (TPJ), superior temporal gyrus (STG), and limbic/paralimbic regions. Besides commonality, our findings showed some distinct abnormalities in ASD children with SHANK3 defects compared to those without. Locally, more changes in the STG and orbitofrontal cortex were exhibited in ASD children with SHANK3 defects, while more changes in the TPJ and inferior parietal lobe (IPL) in those without SHANK3 defects were observed. For the SCNs, a trend toward regular network topology was observed in ASD children with SHANK3 defects, but not in those without. In addition, ASD children with SHANK3 defects showed more alterations of nodal degrees in the anterior and posterior cingulate cortices and right insular, while there were more disruptions in the sensorimotor areas and the left insular and dorsomedial PFC in ASD without SHANK3 defects. Our findings indicate dissociable disruptions of local and networked brain morphological features in ASD children with and without SHANK3 deficiency. Moreover, this monogenic study may provide a valuable path for parsing the heterogeneity of brain disturbances in ASD.

show abstract

“…Though twin and genome studies have demonstrated that ASC has a genetic component, the genetic basis could be syndromic or non-syndromic. Though syndromic forms account only for 2%–4% of ASC cases, they implicate genes that can then be used to understand underlying cellular processes (Sztainberg and Zoghbi, 2016 ; Ziats et al, 2021 ) in manipulatable rodent models. These genes tend to be very rare within the general population but they have a large effect size in that they are very penetrant (Geschwind, 2011 ).…”

Section: Many Genes Linked To Asc Are Regulators Of Mtorc1 or Targets...mentioning

confidence: 99%

mTOR-Dependent Spine Dynamics in Autism

Chaudry

Vasudevan

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Autism Spectrum Conditions (ASC) are a group of neurodevelopmental disorders characterized by deficits in social communication and interaction as well as repetitive behaviors and restricted range of interests. ASC are complex genetic disorders with moderate to high heritability, and associated with atypical patterns of neural connectivity. Many of the genes implicated in ASC are involved in dendritic spine pruning and spine development, both of which can be mediated by the mammalian target of rapamycin (mTOR) signaling pathway. Consistent with this idea, human postmortem studies have shown increased spine density in ASC compared to controls suggesting that the balance between autophagy and spinogenesis is altered in ASC. However, murine models of ASC have shown inconsistent results for spine morphology, which may underlie functional connectivity. This review seeks to establish the relevance of changes in dendritic spines in ASC using data gathered from rodent models. Using a literature survey, we identify 20 genes that are linked to dendritic spine pruning or development in rodents that are also strongly implicated in ASC in humans. Furthermore, we show that all 20 genes are linked to the mTOR pathway and propose that the mTOR pathway regulating spine dynamics is a potential mechanism underlying the ASC signaling pathway in ASC. We show here that the direction of change in spine density was mostly correlated to the upstream positive or negative regulation of the mTOR pathway and most rodent models of mutant mTOR regulators show increases in immature spines, based on morphological analyses. We further explore the idea that these mutations in these genes result in aberrant social behavior in rodent models that is due to these altered spine dynamics. This review should therefore pave the way for further research on the specific genes outlined, their effect on spine morphology or density with an emphasis on understanding the functional role of these changes in ASC.

show abstract

Syndromic Autism Revisited: Review of the Literature and Lessons Learned

Cited by 36 publications

References 49 publications

Molecular Dysregulation in Autism Spectrum Disorder

Molecular Dysregulation in Autism Spectrum Disorder

Common and Distinct Disruptions of Cortical Surface Morphology Between Autism Spectrum Disorder Children With and Without SHANK3 Deficiency

mTOR-Dependent Spine Dynamics in Autism

Contact Info

Product

Resources

About