1. Drimalla H, Scheffer T, Landwehr N, Baskow I, Roepke S, Behnia B, Dziobek I. Author Correction: Towards the automatic detection of social biomarkers in autism spectrum disorder: introducing the simulated interaction task (SIT). NPJ digital medicine. 2022; 5(1): 20.

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2. Han ST, Kim AC, Garcia K, Schimmenti LA, Macnamara E, Network UD, Gahl WA, Malicdan MC, Tifft CJ. PUS7 deficiency in human patients causes profound neurodevelopmental phenotype by dysregulating protein translation. Molecular genetics and metabolism. 2022; 135(3): 221-9.

Protein translation is a highly regulated process involving the interaction of numerous genes on every component of the protein translation machinery. Upregulated protein translation is a hallmark of cancer and is implicated in autism spectrum disorder, but the risks of developing each disease do not appear to be correlated with one another. In this study we identified two siblings from the NIH Undiagnosed Diseases Program with loss of function variants in PUS7, a gene previously implicated in the regulation of total protein translation. These patients exhibited a neurodevelopmental phenotype including autism spectrum disorder in the proband. Both patients also had features of Lesch-Nyhan syndrome, including hyperuricemia and self-injurious behavior, but without pathogenic variants in HPRT1. Patient fibroblasts demonstrated upregulation of protein synthesis, including elevated MYC protein, but did not exhibit increased rates of cell proliferation. Interestingly, the dysregulation of protein translation also resulted in mildly decreased levels of HPRT1 protein suggesting an association between dysregulated protein translation and the LNS-like phenotypic findings. These findings strengthen the correlation between neurodevelopmental disease, particularly autism spectrum disorders, and the rate of protein translation.

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3. Lundbergh B, Enevoldsen AS, Stark KD, Ritz C, Lauritzen L. Fish oil supplementation may improve attention, working memory and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: a randomised crossover trial. The British journal of nutrition. 2022: 1-11.

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2 × 4 week crossover study, twenty-six participants were randomised to sequence of supplementation with fish oil (FO, 5•2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15 %. Compliance was 94 % and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0•3 × sd (P = 0•032) after FO v. SO, and the odds for d2 errors were 30 % lower (P = 0•016), which was supported by improved Conners scores of attention (P = 0•023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3•5(-6•0; -1•0), n 10 v. -0•2(-2•5;2•2), n 11 without ADHD, Pinteraction = 0•096), who also improved their behavioural regulation index by 0•3 × sd after FO (Pinteraction = 0•016). Participants without ADHD gained most in d2 test performance (OR = 0•4(0•2;0•7) v. 0•9(0•6;1•3) in those with ADHD, Pinteraction = 0•002), but their executive function score was exacerbated after FO (5•9(0•0,11•8), Pinteraction = 0•039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.

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4. Mammarella V, Arigliani E, Giovannone F, Cavalli G, Tofani M, Sogos C. Is it hyperlexia? Toward a deeper understanding of precocious reading skills in two cases of children with Autism Spectrum Disorder. La Clinica terapeutica. 2022; 173(1): 15-21.

BACKGROUND: Hyperlexia is defined by a precocious and sponta-neously acquired ability to read at preschool age. Hyperlexia appears to be a wide yet not highly studied phenomenon involving different populations and possibly including children with different neuropsy-chological profiles and outcomes. METHODS: We describe two clinical cases of unrelated children diagnosed with Autism Spectrum Disorder (ASD) who both showed precocious and spontaneous reading ability. We report the neuropsy-chological assessment they underwent. RESULTS: Both children showed above average IQ, reading skills, and text comprehension, whereas one showed below average comprehen-sion only in oral text. We question whether these two phenotypes can be considered forms of hyperlexia, as defined by the most recent and consistent observations, or a subtype of ASD with hyperlexia. CONCLUSION: We conclude that our patients should be considered hyperlexic ASD, with interesting potential implications for progno-sis and rehabilitation.

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5. Masefield SC, Prady SL, Pickett KE. An approach to identifying young children with developmental disabilities via primary care records. Wellcome open research. 2021; 6: 189.

Background: Preschool aged children with developmental disabilities frequently receive a diagnosis of an indicator of disability, such as developmental delay, some time before receiving a definitive diagnosis at school age, such as autism spectrum disorder. The absence of a definitive diagnosis potentially underestimates the need for support by families with young disabled children, also delaying the access of families to condition-specific information and support. Our aim was to develop a strategy to identify children with probable and potential developmental disabilities before the age of five in primary care records for a UK birth cohort, considering how the identification of only probable or potential developmental disability might influence prevalence estimates. Methods: As part of a study of the effects of caring for young children with developmental disabilities on mothers’ health and healthcare use, we developed a two-part strategy to identify: 1) children with conditions associated with significant disability and which can be diagnosed during the preschool period; and 2) children with diagnoses which could indicate potential disability, such as motor development disorder. The strategy, using Read codes, searched the electronic records of children in the Born in Bradford cohort with linked maternal and child sociodemographic information. The results were compared with national and Bradford prevalence estimates. Results: We identified 83 children with disability conditions and 394 with potential disability (44 children had a disability condition and an indicator of potential disability). Combined they produced a developmental disability prevalence of 490 per 10,000 which is above the UK estimate for developmental disabilities in children under five (468 per 10,000) and within the 419-505 per 10,000 prevalence estimated for Bradford (for children aged 0-18). Conclusions: When disability prevalence is estimated only using conditions diagnosed as developmental disabilities, most young children with developmental disabilities likely to be diagnosed at later ages will be missed.

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6. Meng L, Kaufmann WE, Frye RE, Ong K, Kaminski JW, Velinov M, Berry-Kravis E. The association between mosaicism type and cognitive and behavioral functioning among males with fragile X syndrome. American journal of medical genetics Part A. 2022; 188(3): 858-66.

Mosaicism in fragile X syndrome (FXS) refers to two different FMR1 allele variations: size mosaicism represents different numbers of CGG repeats between the two alleles, such that in addition to a full mutation allele there is an allele in the normal or premutation range of CGG repeats, while methylation mosaicism indicates whether a full-mutation allele is fully or partially methylated. The present study explored the association between mosaicism type and cognitive and behavioral functioning in a large sample of males 3 years and older (n = 487) with FXS, participating in the Fragile X Online Registry with Accessible Research Database. Participants with methylation mosaicism were less severely cognitively affected as indicated by a less severe intellectual disability rating, higher intelligence quotient and adaptive behavior score, and lower social impairment score. In contrast, the presence of size mosaicism was not significantly associated with better cognitive and behavioral outcomes than full mutation. Our findings suggest that methylation mosaicism is associated with better cognitive functioning and adaptive behavior and less social impairment. Further research could assess to what extent these cognitive and behavioral differences depend on molecular diagnostic methods and the impact of mosaicism on prognosis of individuals with FXS.

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7. Rigby MJ, Orefice NS, Lawton AJ, Ma M, Shapiro SL, Yi SY, Dieterich IA, Frelka A, Miles HN, Pearce RA, Yu JPJ, Li L, Denu JM, Puglielli L. SLC13A5/sodium-citrate co-transporter overexpression causes disrupted white matter integrity and an autistic-like phenotype. Brain communications. 2022; 4(1): fcac002.

Endoplasmic reticulum-based N (ɛ)-lysine acetylation serves as an important protein quality control system for the secretory pathway. Dysfunctional endoplasmic reticulum-based acetylation, as caused by overexpression of the acetyl coenzyme A transporter AT-1 in the mouse, results in altered glycoprotein flux through the secretory pathway and an autistic-like phenotype. AT-1 works in concert with SLC25A1, the citrate/malate antiporter in the mitochondria, SLC13A5, the plasma membrane sodium/citrate symporter and ATP citrate lyase, the cytosolic enzyme that converts citrate into acetyl coenzyme A. Here, we report that mice with neuron-specific overexpression of SLC13A5 exhibit autistic-like behaviours with a jumping stereotypy. The mice displayed disrupted white matter integrity and altered synaptic structure and function. Analysis of both the proteome and acetyl-proteome revealed unique adaptations in the hippocampus and cortex, highlighting a metabolic response that likely plays an important role in the SLC13A5 neuron transgenic phenotype. Overall, our results support a mechanistic link between aberrant intracellular citrate/acetyl coenzyme A flux and the development of an autistic-like phenotype.

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8. Scarselli V, Martucci M, Prono F, Giovannone F, Sogos C. Sleep behavior of children with Autism Spectrum Disorder during the Covid-19 pandemic: A Parent survey. La Clinica terapeutica. 2022; 173(1): 88-90.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a group of neurodevelopmental conditions characterized by social interaction and communication deficits and restricted, repetitive interests and behaviors (1). It is very common for children with ASD to present with several comorbidities, including sleep disorders. During the Covid-19 pandemic, children with ASD have been particularly at risk of adverse effects because of their difficulties in adapting to changes in daily habits and routines. METHODS AND AIM: Therefore, the aim of our study was to investigate sleep habits during the Covid-19 pandemic by administering the Child Sleep Habits Questionnaire (CSHQ) to parents. RESULTS: Twenty-five children of 28 (89.3%) had a score above 41 during the pandemic. Of these, 11 children also had clinically signifi-cant scores before the pandemic. DISCUSSION: Our data confirm that sleep disturbances have been very common in autistic children during the Covid-19 pandemic and suggest new considerations. In particular, in our clinical sample, sleep habits seemed to improve or not change significantly during the Covid-19 pandemic in a population with a high prevalence of cli-nically significant sleep disturbances. These data confirm that in this particular context, a supportive environment (family, parent training, tele-rehabilitation) is very important for autistic people and a predicta-ble routine can help prevent stress, anxiety, and behavioral problems.

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9. Xie Y, Xu Z, Xia M, Liu J, Shou X, Cui Z, Liao X, He Y. Alterations in Connectome Dynamics in Autism Spectrum Disorder: A Harmonized Mega- and Meta-analysis Study Using the Autism Brain Imaging Data Exchange Dataset. Biological psychiatry. 2021.

BACKGROUND: Neuroimaging studies have reported functional connectome aberrancies in autism spectrum disorder (ASD). However, the time-varying patterns of connectome topology in individuals with ASD and the connection between these patterns and gene expression profiles remain unknown. METHODS: To investigate case-control differences in dynamic connectome topology, we conducted mega- and meta-analyses of resting-state functional magnetic resonance imaging data of 939 participants (440 patients with ASD and 499 healthy control subjects, all males) from 18 independent sites, selected from the Autism Brain Imaging Data Exchange (ABIDE) dataset. Functional data were preprocessed and analyzed using harmonized protocols, and brain module dynamics was assessed using a multilayer network model. We further leveraged postmortem brain-wide gene expression data to identify transcriptomic signatures associated with ASD-related alterations in brain dynamics. RESULTS: Compared with healthy control participants, individuals with ASD exhibited a higher global mean and lower standard deviation of whole-brain module dynamics, indicating an unstable and less regionally differentiated pattern. More specifically, individuals with ASD showed higher module switching, primarily in the medial prefrontal cortex, posterior cingulate gyrus, and angular gyrus, and lower switching in the visual regions. These alterations in brain dynamics were predictive of social impairments in individuals with ASD and were linked with expression profiles of genes primarily involved in the regulation of neurotransmitter transport and secretion as well as with previously identified autism-related genes. CONCLUSIONS: This study is the first to identify consistent alterations in brain network dynamics in ASD and the transcriptomic signatures related to those alterations, furthering insights into the biological basis behind this disorder.

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