1. Al Saad AJ, Alhassan GM, Albedaiwi MS, Alqattan FF, Alessa FA, Alabdulmohsen HW. Acceptance of COVID-19 vaccination among parents of children with autism and other neurodevelopmental disorders in Saudi Arabia: a cross-sectional study. BMC public health. 2023; 23(1): 1235.

BACKGROUND: Acceptance of COVID-19 vaccination was noticed to be less common among parents of children with autism spectrum disorder (ASD) and other neurodevelopmental disorders. This study aimed to explore the beliefs and willingness of parents of children with neurodevelopmental disorders about COVID-19 vaccine and understand how certain factors influencing the vaccine decision-making process differ between them and other parents’ groups. METHODS: A cross-sectional study was conducted between August to November 2021. An Arabic online survey was distributed in August 2021 to collect the study’s data. 400 parents from all the major regions in Saudi Arabia participated in and shared their beliefs about the new COVID-19 vaccination for their children. RESULTS: Out of 400 participants, 381 of them were eligible to answer the survey (95.2%). The total number of parents of children with neurodevelopmental disorder was 158 (41.5%), was compared to responses of parents of heathy children 223 (58.5%). 85 (53.8%) of them were ready to vaccinate their children with COVID-19 vaccine. While 36 (22.8%) were hesitant, the rest 37 (23.4%) did not want to vaccinate their children at all. Only a small number 16 (10.1%) have beliefs of vaccines as a cause of their child’s neurodevelopmental disorder. A total of 79 out of 131 responses were received from both parents’ groups. Fear of long-term side-effects was the most common reason reported by 41 responders out of 64 (64.06%) from parents of healthy children and 38 responders out of 67 (56.71%) from parents of diagnosed children. Another reason reported by parents of younger children in both groups was the child’s age. Having a healthcare relative worker was significantly associated with the vaccine decision making (p < .001). CONCLUSION: The acceptance rate of COVID-19 vaccination of parents of children with neurodevelopmental disorders was low compared to the parents of healthy children in Saudi Arabia. Authorities can benefit from this study results to offer more accessible information about the vaccine importance and safety to the targeted population.

Lien vers le texte intégral (Open Access ou abonnement)

2. Algahtani MM, Ahmad SF, Alkharashi LA, Al-Harbi NO, Alanazi WA, Alhamed AS, Attia SM, Bakheet SA, Ibrahim KE, Nadeem A. Exposure to Methylmercury at Juvenile Stage Worsens Autism-like Symptoms in Adult BTBR T+tf/J Mice Due to Lack of Nuclear Factor Erythroid 2-Related Factor 2 Signaling Upregulation in Periphery and Brain. Toxics. 2023; 11(6).

Autism spectrum disorder (ASD) is a multifaceted developmental condition that first appears in infancy. The condition is characterized by recurrent patterns in behavior and impairments in social and vocalization abilities. Methylmercury is a toxic environmental pollutant, and its derivatives are the major source of organic mercury to human beings. Inorganic mercury, which is released from a variety of pollutants into oceans, rivers, and streams, is transformed into methylmercury by bacteria and plankton in the water, which later builds up in fish and shellfish, and then enters humans through the consumption of fish and shellfish and increases the risk of developing ASD by disturbing the oxidant-antioxidant balance. However, there has been no prior research to determine the effect of juvenile exposure of methylmercury chloride on adult BTBR mice. Therefore, the current study evaluated the effect of methylmercury chloride administered during the juvenile stage on autism-like behavior (three-chambered sociability, marble burying, self-grooming tests) and oxidant-antioxidant balance (specifically Nrf2, HO-1, SOD-1, NF-kB, iNOS, MPO, and 3-nitrotyrosine) in the peripheral neutrophils and cortex of adult BTBR and C57BL/6 (B6) mice. Our results show that exposure to methylmercury chloride at a juvenile stage results in autism-like symptoms in adult BTBR mice which are related to a lack of upregulation of the Nrf2 signaling pathway as demonstrated by no significant changes in the expression of Nrf2, HO-1, and SOD-1 in the periphery and cortex. On the other hand, methylmercury chloride administration at a juvenile stage increased oxidative inflammation as depicted by a significant increase in the levels of NF-kB, iNOS, MPO, and 3-nitrotyrosine in the periphery and cortex of adult BTBR mice. This study suggests that juvenile exposure to methylmercury chloride contributes to the worsening of autism-like behavior in adult BTBR mice through the disruption of the oxidant-antioxidant balance in the peripheral compartment and CNS. Strategies that elevate Nrf2 signaling may be useful to counteract toxicant-mediated worsening of ASD and may improve quality of life.

Lien vers le texte intégral (Open Access ou abonnement)

3. Alsubaiei SRM, Alfawaz HA, Bhat RS, El-Ansary A. Nutritional Intervention as a Complementary Neuroprotective Approach against Propionic Acid-Induced Neurotoxicity and Associated Biochemical Autistic Features in Rat Pups. Metabolites. 2023; 13(6).

Since there is no known cure for autism spectrum disorder (ASD), its incidence rate is on the rise. Common comorbidities like gastrointestinal problems are observed as common signs of ASD and play a major role in controlling social and behavioral symptoms. Although there is a lot of interest in dietary treatments, no harmony exists with regard to the ideal nutritional therapy. To better direct prevention and intervention measures for ASD, the identification of risk and protective factors is required. Through the use of a rat model, our study aims to assess the possible danger of exposure to neurotoxic doses of propionic acid (PPA) and the nutritional protective effects of prebiotics and probiotics. Here, we conducted a biochemical assessment of the effects of dietary supplement therapy in the PPA model of autism. We used 36 male Sprague Dawley albino rat pups divided into six groups. Standard food and drink were given to the control group. The PPA-induced ASD model was the second group; it was fed a conventional diet for 27 days before receiving 250 mg/kg of PPA orally for three days. The four other groups were given 3 mL/kg of yoghurt daily, 400 mg/Kg of artichokes daily, 50 mg/kg of luteolin daily and Lacticaseibacillus rhamnosus GG at 0.2 mL daily for 27 days before being given PPA (250 mg/kg BW) for three days along with their normal diet. All groups had their brain homogenates tested for biochemical markers, which included gamma-aminobutyric acid (GABA), glutathione peroxidase 1 (GPX1), glutathione (GSH), interleukin 6 (IL-6), interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF). When compared with the control group, the PPA-induced model presented increased oxidative stress and neuroinflammation but groups treated with all four dietary therapies presented improvements in biochemical characteristics for oxidative stress and neuroinflammation. As all of the therapies show sufficient anti-inflammatory and antioxidant effects, they can be used as a useful dietary component to help prevent ASD.

Lien vers le texte intégral (Open Access ou abonnement)

4. Benabdallah FZ, Drissi El Maliani A, Lotfi D, El Hassouni M. A Convolutional Neural Network-Based Connectivity Enhancement Approach for Autism Spectrum Disorder Detection. Journal of imaging. 2023; 9(6).

Autism spectrum disorder (ASD) represents an ongoing obstacle facing many researchers to achieving early diagnosis with high accuracy. To advance developments in ASD detection, the corroboration of findings presented in the existing body of autism-based literature is of high importance. Previous works put forward theories of under- and over-connectivity deficits in the autistic brain. An elimination approach based on methods that are theoretically comparable to the aforementioned theories proved the existence of these deficits. Therefore, in this paper, we propose a framework that takes into account the properties of under- and over-connectivity in the autistic brain using an enhancement approach coupled with deep learning through convolutional neural networks (CNN). In this approach, image-alike connectivity matrices are created, and then connections related to connectivity alterations are enhanced. The overall objective is the facilitation of early diagnosis of this disorder. After conducting tests using information from the large multi-site Autism Brain Imaging Data Exchange (ABIDE I) dataset, the results show that this approach provides an accurate prediction value reaching up to 96%.

Lien vers le texte intégral (Open Access ou abonnement)

5. Chiapperino L, Hens K. How to talk about autism: reconciling genomics and neurodiversity. Nature medicine. 2023.

Lien vers le texte intégral (Open Access ou abonnement)

6. Fukui N, Watanabe Y, Motegi T, Hashijiri K, Ogawa M, Egawa J, Enomoto T, Someya T. Relationships among autistic traits, depression, anxiety, and maternal-infant bonding in postpartum women. BMC psychiatry. 2023; 23(1): 463.

BACKGROUND: Although several studies have found significant relationships between autistic traits and depression/anxiety, the relationships between autistic traits and postpartum depression/anxiety remain unclear. Moreover, few studies have examined the relationships between autistic traits and mother-infant bonding while considering depression or anxiety. METHODS: This study used a cross-sectional data analysis design. Participants were 2692 women who completed the Autism-Spectrum Quotient (AQ), Hospital Anxiety and Depression Scale (HADS), and Mother-to-Infant Bonding Scale (MIBS) at 1 month postpartum. We performed path analysis that included parity, the five AQ subscales (social skills, attention switching, attention to detail, communication, and imagination), both HADS subscales (anxiety and depression), and the two MIBS subscales (lack of affection and anger and rejection). RESULTS: Our path analysis revealed that higher scores for social skills, attention switching, communication, and imagination were associated with higher scores for depression. Higher scores for social skills, attention switching, attention to detail, and communication were associated with higher scores for anxiety. Moreover, difficulties in social skills and imagination were associated with failure of maternal-infant bonding. However, more attention to detail was associated with better maternal-infant bonding. CONCLUSIONS: This study suggests that maternal autistic traits are related to anxiety and depression to a certain degree, but only slightly related to maternal-infant bonding at 1 month postpartum. To improve autistic women’s quality of life and that of their newborns, perinatal mental health issues such as anxiety, depression, and maternal-fetal bonding difficulties should be appropriately addressed.

Lien vers le texte intégral (Open Access ou abonnement)

7. Guo Y, Shen M, Dong Q, Méndez-Albelo NM, Huang SX, Sirois CL, Le J, Li M, Jarzembowski ED, Schoeller KA, Stockton ME, Horner VL, Sousa AMM, Gao Y, Levine JE, Wang D, Chang Q, Zhao X. Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway. Nature communications. 2023; 14(1): 3801.

Fragile X messenger ribonucleoprotein 1 protein (FMRP) binds many mRNA targets in the brain. The contribution of these targets to fragile X syndrome (FXS) and related autism spectrum disorder (ASD) remains unclear. Here, we show that FMRP deficiency leads to elevated microtubule-associated protein 1B (MAP1B) in developing human and non-human primate cortical neurons. Targeted MAP1B gene activation in healthy human neurons or MAP1B gene triplication in ASD patient-derived neurons inhibit morphological and physiological maturation. Activation of Map1b in adult male mouse prefrontal cortex excitatory neurons impairs social behaviors. We show that elevated MAP1B sequesters components of autophagy and reduces autophagosome formation. Both MAP1B knockdown and autophagy activation rescue deficits of both ASD and FXS patients’ neurons and FMRP-deficient neurons in ex vivo human brain tissue. Our study demonstrates conserved FMRP regulation of MAP1B in primate neurons and establishes a causal link between MAP1B elevation and deficits of FXS and ASD.

Lien vers le texte intégral (Open Access ou abonnement)

8. Kiffmeyer EA, Cosgrove JA, Siganos JK, Bien HE, Vipond JE, Vogt KR, Kloth AD. Deficits in cerebellum-dependent learning and cerebellar morphology in male and female BTBR autism model mice. NeuroSci. 2022; 3(4): 624-44.

Recently, there has been increased interest in the role of the cerebellum in autism spectrum disorders (ASD). To better understand the pathophysiological role of the cerebellum in ASD, it is necessary to have a variety of mouse models that have face validity for cerebellar disruption in humans. Here, we add to the literature on the cerebellum transgenic and induced mouse models of autism with the characterization of the cerebellum in the BTBR T+Itpr3(tf)/J (BTBR) inbred mouse strain, which has behavioral phenotypes that are suggestive of ASD in patients. When we examined both male and female BTBR mice in comparison to C57BL/6J (C57) controls, we noted that both sexes of BTBR mice showed motor coordination deficits characteristic of cerebellar dysfunction, but only the male mice showed differences in delay eyeblink conditioning, a cerebellum-dependent learning task that is also disrupted in ASD patients. Both male and female BTBR mice showed considerable expansion of and abnormal foliation in the cerebellum vermis–including significant expansion of specific lobules in the anterior cerebellum. In addition, we found a slight but significant decrease in Purkinje cell density in both male and female BTBR mice, irrespective of lobule. Furthermore, there was a marked reduction of Purkinje cell dendritic spines density in both male and female BTBR mice. These findings suggest that, for the most part, the BTBR mouse model successfully phenocopies many of the characteristics of the subpopulation of ASD patients that have a hypertrophic cerebellum. We discuss the significance of strain differences in the cerebellum as well as the importance of this first effort to identify both concordances and difference between male and female BTBR mice with regard to the cerebellum.

Lien vers le texte intégral (Open Access ou abonnement)

9. Lasser M, Sun N, Xu Y, Wang S, Drake S, Law K, Gonzalez S, Wang B, Drury V, Castillo O, Zaltsman Y, Dea J, Bader E, McCluskey KE, State MW, Willsey AJ, Willsey HR. Pleiotropy of autism-associated chromatin regulators. Development (Cambridge, England). 2023.

Gene ontology analyses of high-confidence autism spectrum disorder (ASD) risk genes highlight chromatin regulation and synaptic function as major contributors to pathobiology. Our recent functional work in vivo has additionally implicated tubulin biology and cellular proliferation. As many chromatin regulators, including ASD risk genes ADNP and CHD3, are known to directly regulate both tubulins and histones, we studied the five chromatin regulators most strongly associated with ASD (ADNP, CHD8, CHD2, POGZ, and KMT5B) specifically with respect to tubulin biology. We observe that all five localize to microtubules of the mitotic spindle in vitro and in vivo. Investigation of CHD2 provides evidence that patient-derived mutations cause a range of microtubule-related phenotypes, including disrupted localization of the protein at mitotic spindles, cell cycle stalling, DNA damage, and cell death. Lastly, we observe that ASD genetic risk is significantly enriched among tubulin-associated proteins, suggesting broader relevance. Together, these results provide additional evidence that the role of tubulin biology and cellular proliferation in ASD warrants further investigation and highlight the pitfalls of relying solely on annotated gene functions in the search for pathological mechanisms.

Lien vers le texte intégral (Open Access ou abonnement)

10. Lu H, Zuo L, Roddick KM, Zhang P, Oku S, Garden J, Ge Y, Bellefontaine M, Delhaye M, Brown RE, Craig AM. Alternative splicing and heparan sulfation converge on neurexin-1 to control glutamatergic transmission and autism-related behaviors. Cell reports. 2023; 42(7): 112714.

Neurexin synaptic organizing proteins are central to a genetic risk pathway in neuropsychiatric disorders. Neurexins also exemplify molecular diversity in the brain, with over a thousand alternatively spliced forms and further structural heterogeneity contributed by heparan sulfate glycan modification. Yet, interactions between these modes of post-transcriptional and post-translational modification have not been studied. We reveal that these regulatory modes converge on neurexin-1 splice site 5 (S5): the S5 insert increases the number of heparan sulfate chains. This is associated with reduced neurexin-1 protein level and reduced glutamatergic neurotransmitter release. Exclusion of neurexin-1 S5 in mice boosts neurotransmission without altering the AMPA/NMDA ratio and shifts communication and repetitive behavior away from phenotypes associated with autism spectrum disorders. Thus, neurexin-1 S5 acts as a synaptic rheostat to impact behavior through the intersection of RNA processing and glycobiology. These findings position NRXN1 S5 as a potential therapeutic target to restore function in neuropsychiatric disorders.

Lien vers le texte intégral (Open Access ou abonnement)

11. Morsanyi K, Hamilton J. The Development of Intuitive and Analytic Thinking in Autism: The Case of Cognitive Reflection. Journal of Intelligence. 2023; 11(6).

The cognitive reflection test (CRT) is a short measure of a person’s ability to resist intuitive response tendencies, and to produce normatively correct responses that are assumed to be based on effortful, analytic thinking. A remarkable characteristic of the CRT is that although the questions are open-ended, for each item, the vast majority of people either produce a correct, analytic response or a typical incorrect (i.e., intuitive) response. This unique feature of the CRT makes it possible to investigate the question of whether autistic and neurotypical people share the same intuitions. We report a study that included adolescents and young adults. In both age groups, autistic and neurotypical participants were matched on age, gender, cognitive ability, and educational background. In line with previous findings, the results showed an age-related increase in analytic responding on the CRT, and a decrease in intuitive responding. Crucially, the proportion of both intuitive and analytic responses across autistic and neurotypical participants was identical in both age groups. The current results are in contrast with claims that autistic individuals have an increased tendency toward an analytic/rational type of processing, which is commonly attributed to an impairment within their intuitive reasoning mechanisms.

Lien vers le texte intégral (Open Access ou abonnement)

12. Morton JT, Jin DM, Mills RH, Shao Y, Rahman G, McDonald D, Zhu Q, Balaban M, Jiang Y, Cantrell K, Gonzalez A, Carmel J, Frankiensztajn LM, Martin-Brevet S, Berding K, Needham BD, Zurita MF, David M, Averina OV, Kovtun AS, Noto A, Mussap M, Wang M, Frank DN, Li E, Zhou W, Fanos V, Danilenko VN, Wall DP, Cárdenas P, Baldeón ME, Jacquemont S, Koren O, Elliott E, Xavier RJ, Mazmanian SK, Knight R, Gilbert JA, Donovan SM, Lawley TD, Carpenter B, Bonneau R, Taroncher-Oldenburg G. Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles. Nature neuroscience. 2023.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.

Lien vers le texte intégral (Open Access ou abonnement)

13. Razzaq A, Bejaoui Y, Alam T, Saad M, El Hajj N. Ribosomal DNA Copy Number Variation is Coupled with DNA Methylation Changes at the 45S rDNA Locus. Epigenetics. 2023; 18(1): 2229203.

The human ribosomal DNA (rDNA) copy number (CN) has been challenging to analyse, and its sequence has been excluded from reference genomes due to its highly repetitive nature. The 45S rDNA locus encodes essential components of the cell, nevertheless rDNA displays high inter-individual CN variation that could influence human health and disease. CN alterations in rDNA have been hypothesized as a possible factor in autism spectrum disorders (ASD) and were shown to be altered in Schizophrenia patients. We tested whether whole-genome bisulphite sequencing can be used to simultaneously quantify rDNA CN and measure DNA methylation at the 45S rDNA locus. Using this approach, we observed high inter-individual variation in rDNA CN, and limited intra-individual copy differences in several post-mortem tissues. Furthermore, we did not observe any significant alterations in rDNA CN or DNA methylation in Autism Spectrum Disorder (ASD) brains in 16 ASD vs 11 control samples. Similarly, no difference was detected when comparing neurons form 28 Schizophrenia (Scz) patients vs 25 controls or oligodendrocytes from 22 Scz samples vs 20 controls. However, our analysis revealed a strong positive correlation between CN and DNA methylation at the 45S rDNA locus in multiple tissues. This was observed in brain and confirmed in small intestine, adipose tissue, and gastric tissue. This should shed light on a possible dosage compensation mechanism that silences additional rDNA copies to ensure homoeostatic regulation of ribosome biogenesis.

Lien vers le texte intégral (Open Access ou abonnement)

14. Rolland T, Cliquet F, Anney RJL, Moreau C, Traut N, Mathieu A, Huguet G, Duan J, Warrier V, Portalier S, Dry L, Leblond CS, Douard E, Amsellem F, Malesys S, Maruani A, Toro R, Børglum AD, Grove J, Baron-Cohen S, Packer A, Chung WK, Jacquemont S, Delorme R, Bourgeron T. Phenotypic effects of genetic variants associated with autism. Nature medicine. 2023.

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants.

Lien vers le texte intégral (Open Access ou abonnement)

15. Scala M, Biondi L, Serretti A, Fabbri C. Obsessive-Compulsive, Psychotic, and Autism Dimensions Overlap in Real World: A Case Report. Clinical neuropharmacology. 2023.

BACKGROUND: Obsessions, compulsions, and stereotypes are common psychopathological manifestations of obsessive-compulsive, psychotic, and autism spectrum disorders (ASDs). These nosological entities may be present in comorbidity, with relevant clinical difficulties in the differential diagnosis process. Moreover, ASDs are a complex group of disorders, with a childhood onset, which also persist into adulthood and present heterogeneous symptom patterns that could be confused with psychotic disorders. METHODS AND RESULTS: We report a case of a 21-year-old man characterized by sexual and doubt obsessions; disorganized, bizarre, and stereotyped behaviors and compulsions; and social withdrawal, inadequate social skills, visual dispersions, and hypersensitivity to light stimuli. Obsessive and compulsive features were initially included within the differential diagnosis of psychotic and obsessive-compulsive spectrum disorders. However, aforementioned psychopathological elements did not improve when multiple antipsychotic drugs (olanzapine, haloperidol, and lurasidone) were administered in the hypothesis of schizophrenia and even worsened with clozapine therapy at a dose of 100 mg/d. Obsessions and compulsions progressively reduced during the fluvoxamine 14-week treatment paradigm at a dose of 200 mg/d. Considering the persistent deficits in social communication and interactions as well as the restricted interests pattern, a differential diagnostic hypothesis of ASD was formulated, and it was then confirmed at the final evaluation at a third-level health care center. CONCLUSIONS: We discuss similarities and differences in the psychopathology of obsessions, compulsions, and stereotypes in the previously mentioned disorders, to underline factors that can help in the differential diagnosis of similar cases, and consequently in the appropriateness of treatment choice.

Lien vers le texte intégral (Open Access ou abonnement)

16. Wang F, Qi N, Gao Y, Wu D, Zhang M, Zhang Q, Yang K, Peng H, Lei X, Liao S. [Genetic analysis of two children with developmental delay and intellectual disability]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2023; 40(7): 876-80.

OBJECTIVE: To explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People’s Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION: The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

Lien vers le texte intégral (Open Access ou abonnement)

17. Zhuang W, Jia H, Liu Y, Cong J, Chen K, Yao D, Kang X, Xu P, Zhang T. Identification and analysis of autism spectrum disorder via large-scale dynamic functional network connectivity. Autism research : official journal of the International Society for Autism Research. 2023.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with severe cognitive impairment. Several studies have reported that brain functional network connectivity (FNC) has great potential for identifying ASD from healthy control (HC) and revealing the relationships between the brain and behaviors of ASD. However, few studies have explored dynamic large-scale FNC as a feature to identify individuals with ASD. This study used a time-sliding window method to study the dynamic FNC (dFNC) on the resting-state fMRI. To avoid arbitrarily determining the window length, we set a window length range of 10-75 TRs (TR = 2 s). We constructed linear support vector machine classifiers for all window length conditions. Using a nested 10-fold cross-validation framework, we obtained a grand average accuracy of 94.88% across window length conditions, which is higher than those reported in previous studies. In addition, we determined the optimal window length using the highest classification accuracy of 97.77%. Based on the optimal window length, we found that the dFNCs were located mainly in dorsal and ventral attention networks (DAN and VAN) and exhibited the highest weight in classification. Specifically, we found that the dFNC between DAN and temporal orbitofrontal network (TOFN) was significantly negatively correlated with social scores of ASD. Finally, using the dFNCs with high classification weights as features, we construct a model to predict the clinical score of ASD. Overall, our findings demonstrated that the dFNC could be a potential biomarker to identify ASD and provide new perspectives to detect cognitive changes in ASD.

Lien vers le texte intégral (Open Access ou abonnement)