Autism Symptoms in Fragile X Syndrome

Niu, Manman; Han, Ying; Dy, Angel Belle C.; Du, Junbao; Huang, Jin; Qin, Jiong; Zhang, Jing; Li, Qinrui; Hagerman, Randi J

doi:10.1177/0883073817712875

Cited by 77 publications

(61 citation statements)

References 46 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In other aspect, Fragile-X syndrome (MIM#30064) is caused by an expansion repeat of CGG in the 5′ UTR of the FMR1 gene. This syndrome is a common comorbid condition with ASD as well as ID [39][40][41] . Therefore, we next screened for this syndrome in all 100 children with ASD.…”

Section: Screening Of Rett and Fragile-x Syndromementioning

confidence: 99%

Genetic landscape of autism spectrum disorder in Vietnamese children

Tran

Bui

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children.Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that includes autism, Asperger's syndrome and pervasive developmental disorder not otherwise specified and is characterized by restricted repetitive behaviour, delays in language development and lack of reciprocal social communication and interaction 1 . The common psychiatric and cognitive comorbidities with ASD include intellectual disability (ID) 2-4 , sleep deprivation 5,6 and epilepsy (EP) 3,7 .Recent studies have gradually emphasized the role of genetics in ASD, with up to 25% of ASD cases having genetically identifiable causes 8 . Males have a 4-fold higher incidence of ASD than females 9 , suggesting the involvement of genetics in the aetiology of ASD. Previous studies have shown that 5% to 15% of patients with ASD have inherited copy number variations (CNVs) or de novo CNVs in some affected genes with synaptic function 10 . Genome-wide association studies have indicated that common variations are risk factors for ASD 11,12 . Meanwhile, de novo CNV and loss of function (LoF) mutations merely explain 2.6% of the variance in liability 12 . Other studies have revealed that non-coding de novo mutations in the promoter regions also affect ASD 13,14 . Recent genomic studies with large samples have explored new genes linked to ASD 15,16 . To date, over 100 genes have been identified as strongly linked to the risk of ASD 17,18 and enriched in the following three main pathways: chromatin remodelling, transcription and splicing, and synaptic function [18][19][20] . In fact, ASD is highly genetically heterogeneous due to multiple familial inheritance patterns and the occurrence of a large number of de novo variations. It is estimated that up to 1000 genes are potentially implicated ASD 21,22 , making it one of the most complex disorders. G...

show abstract

Section: Screening Of Rett and Fragile-x Syndromementioning

confidence: 99%

Genetic landscape of autism spectrum disorder in Vietnamese children

Tran

Bui

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…F r a g i l e X s y n d r o m e ( F X S ) i s t h e c o m m o n neurodevelopmental disease that often co-occurs with autism spectrum disorder (ASD) and is then described as syndromic autism [27]. FXS results from CGG repeat expansion in the 5′ UTR of FMR1 gene, which causes FMR1 gene silencing and the absence of fragile X mental retardation protein (FMRP) [28].…”

Section: Introductionmentioning

confidence: 99%

Neuroligin 1, 2, and 3 Regulation at the Synapse: FMRP-Dependent Translation and Activity-Induced Proteolytic Cleavage

et al. 2018

View full text Add to dashboard Cite

Neuroligins (NLGNs) are cell adhesion molecules located on the postsynaptic side of the synapse that interact with their presynaptic partners neurexins to maintain trans-synaptic connection. Fragile X syndrome (FXS) is a common neurodevelopmental disease that often co-occurs with autism and is caused by the lack of fragile X mental retardation protein (FMRP) expression. To gain an insight into the molecular interactions between the autism-related genes, we sought to determine whether FMRP controls the synaptic levels of NLGNs. We show evidences that FMRP associates with Nlgn1, Nlgn2, and Nlgn3 mRNAs in vitro in both synaptoneurosomes and neuronal cultures. Next, we confirm local translation of Nlgn1, Nlgn2, and Nlgn3 mRNAs to be synaptically regulated by FMRP. As a consequence of elevated Nlgns mRNA translation Fmr1 KO mice exhibit increased incorporation of NLGN1 and NLGN3 into the postsynaptic membrane. Finally, we show that neuroligins synaptic level is precisely and dynamically regulated by their rapid proteolytic cleavage upon NMDA receptor stimulation in both wild type and Fmr1 KO mice. In aggregate, our study provides a novel approach to understand the molecular basis of FXS by linking the dysregulated synaptic expression of NLGNs with FMRP.

show abstract

“…Depending on the research criteria and assessment measures used, studies have reported that 30% to 54% of males with FXS meet the diagnostic criteria for ASD compared to 16% to 20% of females [16][17][18][19][20][21][22][23]. Studies evaluating the features differentiating ASD in FXS have described lower verbal-IQ, receptive language skills, and theory of mind performance [24], as well as more significant behavioral problems [25]. Other phenotypic features of FXS, such as adaptive behavior, cognition, and repetitive behaviors, were not found to differentiate between young children with and without autism [26].…”

Section: Introductionmentioning

confidence: 99%

Evaluating Social Interactions Using the Autism Screening Instrument for Education Planning-3rd Edition (ASIEP-3): Interaction Assessment in Children and Adults with Fragile X Syndrome

et al. 2020

View full text Add to dashboard Cite

An efficient and direct measure of social interactions and autism symptoms is needed for fragile X syndrome (FXS) research and clinical care. The Autism Screening Instrument for Educational Planning-Third Edition (ASIEP-3) Interaction assessment is a brief standardized measure that quantifies social responses under different conditions. The feasibility and validity of the ASIEP-3 was evaluated in 26 males and 13 females with FXS, along with cognitive testing and behavior questionnaires. The videos were scored at 10-second intervals, and the observed behaviors were scored as an interaction, independent play, no response, or aggression. In total, 39/41 participants successfully completed the ASIEP-3 (age M = 14.4 ± 10.2), with a range of cognitive abilities (abbreviated IQ (ABIQ) M = 58.9 ± 17.3, median = 50), behaviors (Aberrant Behavior Checklist (ABC) Total M = 37.00 ± 27.3), and autism diagnoses (N = 22/39). Reliable administration was demonstrated by all team members. The mean coded behaviors included interaction (40.6%), independent play (36.8%), no response (21.1%), and aggressive behavior (<10%). The interaction score was negatively correlated with the Social Communication Questionnaire (SCQ) score (p = 0.037), and the profiles differed by autism spectrum disorder (ASD) diagnosis. The intraclass correlation coefficients (ICCs) ranged from 0.79 to 0.93 for master’s level and above. Administration of the ASIEP-3 was feasible for FXS across sex, age, ability, and behavior ratings by a trained research team. Reliable scoring required advanced training in the assessment of social development and FXS experience. The scores correlated to ratings and diagnoses of ASD. The ASIEP-3 shows promise to reliably index social interactions in FXS.

show abstract

Autism Symptoms in Fragile X Syndrome

Cited by 77 publications

References 46 publications

Genetic landscape of autism spectrum disorder in Vietnamese children

Genetic landscape of autism spectrum disorder in Vietnamese children

Neuroligin 1, 2, and 3 Regulation at the Synapse: FMRP-Dependent Translation and Activity-Induced Proteolytic Cleavage

Evaluating Social Interactions Using the Autism Screening Instrument for Education Planning-3rd Edition (ASIEP-3): Interaction Assessment in Children and Adults with Fragile X Syndrome

Contact Info

Product

Resources

About