6p22.3 deletion: report of a patient with autism, severe intellectual disability and electroencephalographic anomalies

Benedetto, Daniela; Vita, Giuseppa Di; Romano, Corrado; Giudice, Mariangela Lo; Vitello, Girolamo Aurelio; Zingale, Marinella; Grillo, Lucia; Castiglia, Lucia; Musumeci, S; Fichera, Marco

doi:10.1186/1755-8166-6-4

Cited by 28 publications

(27 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cic-L −/− mice phenocopy Atxn1 −/− ; Atxn1l −/− mice, confirming that these three proteins indeed function as a complex in vivo 9 . Interestingly, large deletions spanning ATXN1 on chromosome 6p22 have been reported in patients with autism spectrum disorder (ASD), developmental delay/intellectual disability (DD/ID), seizures, and attention deficit/hyperactivity disorder (ADHD) 11–13 , but it is unclear whether the heterozygous loss of ATXN1 or other genes in the deleted region lead to the clinical presentation. In the case of CIC , two different missense mutations have been reported in two isolated cases of intellectual disability 14,15 , but here again it is unclear whether these variants are causative, because there have been no functional studies to confirm the pathogenicity of the reported missense variants in CIC .…”

Section: Introductionmentioning

confidence: 99%

Disruption of the ATXN1–CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans

Lu¹,

Tan²,

Rousseaux³

et al. 2017

Nat Genet

126

168

View full text Add to dashboard Cite

Gain-of function mutations in some genes underlie neurodegenerative conditions whereas loss-of-function mutations have distinct phenotypes. Such appears to be the case with the protein ataxin 1 (ATXN1), which forms a transcriptional repressor complex with capicua (CIC). Gain-of-function of the complex leads to neurodegeneration, but ATXIN1-CIC is also essential for survival. We set out to understand the functions of ATXN1-CIC in the developing forebrain and found that losing the complex results in hyperactivity, impaired learning and memory, and abnormal maturation and maintenance of upper layer cortical neurons. We also found that CIC modulates social interactions in the hypothalamus and medial amygdala. Informed by these neurobehavioral features in mouse mutants, we identified five patients with de novo heterozygous truncating mutations in CIC that share similar clinical features, including intellectual disability, attention deficit/hyperactivity disorder (ADHD), and autism spectrum disorder. Our study demonstrates that loss of ATXN1-CIC complexes causes a spectrum of neurobehavioral phenotypes.

show abstract

Section: Introductionmentioning

confidence: 99%

Disruption of the ATXN1–CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans

Lu¹,

Tan²,

Rousseaux³

et al. 2017

Nat Genet

126

168

View full text Add to dashboard Cite

show abstract

“…In our analysis, Fyn was strongly correlated with ATXN1, a DNA-binding protein that forms a transcriptional repressor complex with capicua (CIC). It has been previously described that the deletion in chromosome 6p22.3-p24.3, which harbors ATXN1, is associated with developmental delay and ASD [77,78]. Moreover, alteration of the ATXN1-CIC complex determines a spectrum of neurobehavioral phenotypes, including intellectual disability, attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder [79].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Abnormal Expression of Prion Disease Gene Pathway in Brains from Patients with Autism Spectrum Disorders

et al. 2020

View full text Add to dashboard Cite

The role of infections in the pathogenesis of autism spectrum disorder (ASD) is still controversial. In this study, we aimed to evaluate markers of infections and immune activation in ASD by performing a meta-analysis of publicly available whole-genome transcriptomic datasets of brain samples from autistic patients and otherwise normal people. Among the differentially expressed genes, no significant enrichment was observed for infectious diseases previously associated with ASD, including herpes simplex virus-1 (HSV-1), cytomegalovirus and Epstein–Barr virus in brain samples, nor was it found in peripheral blood from ASD patients. Interestingly, a significant number of genes belonging to the “prion diseases” pathway were found to be modulated in our ASD brain meta-analysis. Overall, our data do not support an association between infection and ASD. However, the data do provide support for the involvement of pathways related to other neurodegenerative diseases and give input to uncover novel pathogenetic mechanisms underlying ASD.

show abstract

“…The pleiotropic function of JARID2 has been confirmed by the various phenotypes reported, especially regarding the neural and cardiac systems. Jumonji was originally found to be expressed in the brain of developing mice, and several recent reports have linked JARID2 and intellectual disability in human patients: deletions in chromosome 6p22‐p24, which include JARID2, are clinically linked with neurodevelopment disorders . Further characterization is required to understand whether these clinical observations may be explained at a molecular level by association of PRC2 with JARID2.…”

Section: Jarid2mentioning

confidence: 99%

Role of PRC2‐associated factors in stem cells and disease

et al. 2014

View full text Add to dashboard Cite

The Polycomb group (PcG) of proteins form chromatin‐binding complexes with histone‐modifying activity. The two main PcG repressive complexes studied (PRC1 and PRC2) are generally associated with chromatin in its repressed state. PRC2 is responsible for methylation of histone H3 at lysine 27 (H3K27me3), an epigenetic mark that is linked with numerous biological processes, including development, adult homeostasis and cancer. The core canonical complex PRC2, which contains the EZH1/2, SUZ12 and EED proteins, may be extended and functionally manipulated through interactions with several other proteins. In this review, we focus on these PRC2‐associated proteins. As PRC2 functions are diverse, the variability conferred by these sub‐stoichiometrically associated members may help to understand specific changes in PRC2 activity, chromatin recruitment and distribution required for gene repression.

show abstract

6p22.3 deletion: report of a patient with autism, severe intellectual disability and electroencephalographic anomalies

Cited by 28 publications

References 24 publications

Disruption of the ATXN1–CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans

Disruption of the ATXN1–CIC complex causes a spectrum of neurobehavioral phenotypes in mice and humans

Transcriptomic Analysis Reveals Abnormal Expression of Prion Disease Gene Pathway in Brains from Patients with Autism Spectrum Disorders

Role of PRC2‐associated factors in stem cells and disease

Contact Info

Product

Resources

About