Pubmed du 29/11/21
1. Bonsi P, De Jaco A, Fasano L, Gubellini P. Postsynaptic autism spectrum disorder genes and synaptic dysfunction. Neurobiology of disease. 2022; 162: 105564.
This review provides an overview of the synaptic dysfunction of neuronal circuits and the ensuing behavioral alterations caused by mutations in autism spectrum disorder (ASD)-linked genes directly or indirectly affecting the postsynaptic neuronal compartment. There are plenty of ASD risk genes, that may be broadly grouped into those involved in gene expression regulation (epigenetic regulation and transcription) and genes regulating synaptic activity (neural communication and neurotransmission). Notably, the effects mediated by ASD-associated genes can vary extensively depending on the developmental time and/or subcellular site of expression. Therefore, in order to gain a better understanding of the mechanisms of disruptions in postsynaptic function, an effort to better model ASD in experimental animals is required to improve standardization and increase reproducibility within and among studies. Such an effort holds promise to provide deeper insight into the development of these disorders and to improve the translational value of preclinical studies.
Lien vers le texte intégral (Open Access ou abonnement)
2. Borges-Monroy R, Chu C, Dias C, Choi J, Lee S, Gao Y, Shin T, Park PJ, Walsh CA, Lee EA. Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder. Mobile DNA. 2021; 12(1): 28.
BACKGROUND: Retrotransposons have been implicated as causes of Mendelian disease, but their role in autism spectrum disorder (ASD) has not been systematically defined, because they are only called with adequate sensitivity from whole genome sequencing (WGS) data and a large enough cohort for this analysis has only recently become available. RESULTS: We analyzed WGS data from a cohort of 2288 ASD families from the Simons Simplex Collection by establishing a scalable computational pipeline for retrotransposon insertion detection. We report 86,154 polymorphic retrotransposon insertions-including > 60% not previously reported-and 158 de novo retrotransposition events. The overall burden of de novo events was similar between ASD individuals and unaffected siblings, with 1 de novo insertion per 29, 117, and 206 births for Alu, L1, and SVA respectively, and 1 de novo insertion per 21 births total. However, ASD cases showed more de novo L1 insertions than expected in ASD genes. Additionally, we observed exonic insertions in loss-of-function intolerant genes, including a likely pathogenic exonic insertion in CSDE1, only in ASD individuals. CONCLUSIONS: These findings suggest a modest, but important, impact of intronic and exonic retrotransposon insertions in ASD, show the importance of WGS for their analysis, and highlight the utility of specific bioinformatic tools for high-throughput detection of retrotransposon insertions.
Lien vers le texte intégral (Open Access ou abonnement)
3. El-Ansary A, Alhakbany M, Aldbass A, Qasem H, Al-Mazidi S, Bhat RS, Al-Ayadhi L. Correction to: Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values. Lipids in health and disease. 2021; 20(1): 172.
Lien vers le texte intégral (Open Access ou abonnement)
4. Hua R, Xu X, Wu D, Yang L, Yuan J, Zhu J. [Clinical features and genetic analysis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2021; 38(12): 1194-8.
OBJECTIVE: To analyze the clinical features and genetic basis of three children with mental retardation, language impairment and autistic features due to de novo variants of FOXP1 gene. METHODS: Clinical data of the children were collected.Trio-whole exome sequencing was carried out for the children and their parents. Pathogenicity of the variants was analyzed through bioinformatics prediction. RESULTS: All of the children had various degrees of mental retardation in conjunct with language deficit, global developmental delay, abnormal behavior and peculiar facial features, among whom two also developed autism spectrum disorders. The results of genetic testing showed that all three children harbored de novo variants of the FOXP1 gene, namely c.613_c.614delCTinsTA, c.1248delC and c.1393A>G. Two of these were frameshift variants and one was missense variant, which were all rated as pathogenic based on the guidelines of the American College of Medical Genetics (ACMG). Database search suggested that c.613_c.614delCTinsTA and c.1248delC were unreported previously. CONCLUSION: For the three children from unrelated families with mental retardation in conjunct with language deficit, global growth delay, abnormal behavior and peculiar facial features, the c.613_ c. 614delCTinsTA, c.1248delC and c.1393A>G variants of the FOXP1 gene may be the pathogenic factors. Above cases have further expanded the genotype-phenotype profile of FOXP1 deficiency syndrome.
Lien vers le texte intégral (Open Access ou abonnement)
5. Jia X, Li J, Li H, Zhu H, Li H, Xu W, Li N, Xie J. [Analysis of SIK3 gene variation in a boy with autism spectrum disorder complicated with epilepsy]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2021; 38(12): 1228-32.
OBJECTIVE: To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism. METHODS: Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene. RESULTS: The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain. CONCLUSION: The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.
Lien vers le texte intégral (Open Access ou abonnement)
6. Mukerji SS, Rath S, Zhang WQ, Zhu H, Anand GS, Jones JK, Chelius DC, Musso MF, Bedwell JR. Extracapsular versus intracapsular tonsillectomy: Outcomes in children with a focus on developmental delay. International journal of pediatric otorhinolaryngology. 2022; 152: 110978.
INTRODUCTION: Outcomes following intracapsular tonsillectomy (IT) have not been well established in children with developmental delays. The objective of this study was to compare outcomes and complications between intracapsular and extracapsular tonsillectomy (TT) in pediatric patients with developmental delay (DD) in comparison to non-developmentally delayed children. METHODS: This is a retrospective study of pediatric patients with DD undergoing tonsillectomy between 2016 and 2019 at a tertiary care hospital. This group included patients with Down Syndrome, Autism Spectrum Disorder, other genetic syndromes, and patients with a diagnosis of global developmental delay. Outcomes and complications were analyzed for IT and TT. RESULTS: 2267 charts were reviewed, and 320 patients were identified with DD. Of those, 72 patients underwent IT and 248 underwent TT. In the DD cohort, the IT group had a shorter length of stay (0.97 vs 1.7 days, p < .0001) and was less likely to receive post-operative narcotic medication (2.8% vs 35%, p < .0001) and corticosteroids (9.7% vs 64%, p < .0001) during their hospital stay. Reductions in emergency room (ER) visits (5.6% vs 10%, p = .21) and post-op bleeding (PTH) (1.4% vs 4.8%, p = .31) for IT vs TT were not statistically significant in the DD group. In the NDD group, fewer patients undergoing IT returned to the ER (11% vs 2.3%, p < .0001) or had PTH (4.8% vs 0.25%, p, 0.0001) as compared to those children undergoing TT. There was no difference between parental report of symptom improvement between the groups (39% vs 33%, p = .39). Analysis of 180 patients with preoperative and postoperative sleep study data revealed post-op Apnea Hypopnea Index (AHI) improved with both techniques (74% TT vs 79% IT, p = .7). There were no differences noted for persistent obstructive sleep apnea (OSA) among the two techniques for both study groups (p = .63). CONCLUSION: Children with DD undergoing IT have reduced length of stay and reduced inpatient administration of post-operative opioids and steroids. IT has comparable efficacy to TT in treating symptoms of pediatric sleep apnea with a better safety profile. Overall, children undergoing IT return to the operating room less frequently than those undergoing TT. Longer follow-up studies will be needed to evaluate rate of tonsil regrowth, risk of revision surgery and persistence of OSA in these patients.
Lien vers le texte intégral (Open Access ou abonnement)
7. Shaw KA, McArthur D, Hughes MM, Bakian AV, Lee LC, Pettygrove S, Maenner MJ. Progress and Disparities in Early Identification of Autism Spectrum Disorder: Autism and Developmental Disabilities Monitoring Network, 2002-2016. Journal of the American Academy of Child and Adolescent Psychiatry. 2021.
OBJECTIVE: Early identification can improve outcomes for children with autism spectrum disorder (ASD). We sought to assess changes in early ASD identification over time and by co-occurring intellectual disability (ID) and race/ethnicity. METHOD: Using data for 2002 through 2016 from a biennial population-based ASD surveillance program among 8-year-old children in the United States, we defined identification as a child’s earliest recorded ASD diagnosis or special education eligibility. Unidentified children had characteristics meeting the ASD surveillance case definition but no recorded identification by age 8 years. We calculated median age at identification among identified children, median age at identification including unidentified children, and cumulative incidence of identification by age 48 months. RESULTS: ASD identification by age 48 months was 4 times (95% CI: 3.6-4.3) as likely in 2016 as in 2002, with the largest increases among children without ID. Median age at ASD identification among identified children decreased 3 months during this time. Children of every race/ethnicity were more likely to be identified over time. There were racial disparities stratified by ID: in 2016, Black and Hispanic children without ID were less likely to be identified with ASD than were White children (both groups risk ratio: 0.7; 95% CI: 0.5-0.8), but Black children were 1.5 times (95% CI: 1.3-1.9) as likely as White children to be identified with ASD and ID. CONCLUSION: Substantial progress has been made to identify more children with ASD early, despite minimal decrease in median age at diagnosis. Considerable disparities remain in early ASD identification by race/ethnicity and co-occurring intellectual disability.
Lien vers le texte intégral (Open Access ou abonnement)
8. Shephard E, McEwen FS, Earnest T, Friedrich N, Mörtl I, Liang H, Woodhouse E, Tye C, Bolton PF. Oscillatory neural network alterations in young people with tuberous sclerosis complex and associations with co-occurring symptoms of autism spectrum disorder and attention-deficit/hyperactivity disorder. Cortex; a journal devoted to the study of the nervous system and behavior. 2022; 146: 50-65.
Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations on the TSC1/TSC2 genes, which result in alterations in molecular signalling pathways involved in neurogenesis and hamartomas in the brain and other organs. TSC carries a high risk for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), although the reasons for this are unclear. One proposal is that TSC-related alterations in molecular signalling during neurogenesis lead to atypical development of neural networks, which are involved in the occurrence of ASD and ADHD in TSC. We investigated this proposal in young people with TSC who have been studied longitudinally since their diagnosis in childhood. Electroencephalography (EEG) was used to examine oscillatory connectivity in functional neural networks and local and global network organisation during three tasks (resting-state, attentional and inhibitory control Go/Nogo task, upright and inverted face processing task) in participants with TSC (n = 48) compared to an age- and sex-matched group of typically developing Controls (n = 20). Compared to Controls, the TSC group showed hypoconnected neural networks in the alpha frequency during the resting-state and in the theta and alpha frequencies during the Go/Nogo task (P ≤ .008), as well as reduced local network organisation in the theta and alpha frequencies during the Go/Nogo task (F = 3.95, P = .010). There were no significant group differences in network metrics during the face processing task. Increased connectivity in the hypoconnected alpha-range resting-state network was associated with greater ASD and inattentive ADHD symptoms (rho≥.40, P ≤ .036). Reduced local network organisation in the theta-range during the Go/Nogo task was significantly associated with higher hyperactive/impulsive ADHD symptoms (rho = -.43, P = .041). These findings suggest that TSC is associated with widespread hypoconnectivity in neural networks and support the proposal that altered network function may be involved in the co-occurrence of ASD and ADHD in TSC.
Lien vers le texte intégral (Open Access ou abonnement)
9. Zaveri H, Desai J. Thyroid Studies Need to Be Considered for Children With Global Developmental Delay Even With Negative Newborn Screen. Pediatric neurology. 2022; 126: 111.
