1. Asadi-Pooya AA. Electroencephalography in patients with autism spectrum disorder. Brain communications. 2021; 3(4): fcab243.

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2. Broome K, McCabe P, Docking K, Doble M, Carrigg B. Speech Abilities in a Heterogeneous Group of Children With Autism. Journal of speech, language, and hearing research : JSLHR. 2021; 64(12): 4599-613.

PURPOSE: This study aimed to provide detailed descriptive information about the speech of a heterogeneous cohort of children with autism spectrum disorder (ASD) and to explore whether subgroups exist based on this detailed speech data. High rates of delayed and disordered speech in both low-verbal and high-functioning children with ASD have been reported. There is limited information regarding the speech abilities of young children across a range of functional levels. METHOD: Participants were 23 children aged 2;0-6;11 (years;months) with a diagnosis of ASD. Comprehensive speech and language assessments were administered. Independent and relational speech analyses were conducted from single-word naming tasks and spontaneous speech samples. Hierarchical clustering based on language, nonverbal communication, and spontaneous speech descriptive data was completed. RESULTS: Independent and relational speech analyses are reported. These variables are used in the cluster analyses, which identified three distinct subgroups: (a) children with high language and high speech ability (n = 10), (b) children with low expressive language and low speech ability but higher receptive language and use of gestures (n = 3), and (c) children with low language and low speech development (n = 10). CONCLUSIONS: This is the first study to provide detailed descriptive speech data of a heterogeneous cohort of children with ASD and use this information to statistically explore potential subgroups. Clustering suggests a small number of children present with low levels of speech and expressive language in the presence of better receptive language and gestures. This communication profile warrants further exploration. Replicating these findings with a larger cohort of children is needed. Supplemental Material https://doi.org/10.23641/asha.16906978.

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3. Gamal El-Din TM, Lantin T, Tschumi CW, Juarez B, Quinlan M, Hayano JH, Li J, Zweifel LS, Catterall WA. Autism-associated mutations in K(V)7 channels induce gating pore current. Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(45).

Autism spectrum disorder (ASD) adversely impacts >1% of children in the United States, causing social interaction deficits, repetitive behaviors, and communication disorders. Genetic analysis of ASD has advanced dramatically through genome sequencing, which has identified >500 genes with mutations in ASD. Mutations that alter arginine gating charges in the voltage sensor of the voltage-gated potassium (K(V)) channel K(V)7 (KCNQ) are among those frequently associated with ASD. We hypothesized that these gating charge mutations would induce gating pore current (also termed ω-current) by causing an ionic leak through the mutant voltage sensor. Unexpectedly, we found that wild-type K(V)7 conducts outward gating pore current through its native voltage sensor at positive membrane potentials, owing to a glutamine in the third gating charge position. In bacterial and human K(V)7 channels, gating charge mutations at the R1 and R2 positions cause inward gating pore current through the resting voltage sensor at negative membrane potentials, whereas mutation at R4 causes outward gating pore current through the activated voltage sensor at positive potentials. Remarkably, expression of the K(V)7.3/R2C ASD-associated mutation in vivo in midbrain dopamine neurons of mice disrupts action potential generation and repetitive firing. Overall, our results reveal native and mutant gating pore current in K(V)7 channels and implicate altered control of action potential generation by gating pore current through mutant K(V)7 channels as a potential pathogenic mechanism in autism.

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4. Gopal KV, Schafer EC, Nandy R, Brown A, Caldwell J, Phillips B, Ballard G. Characteristic Deviations of Auditory Evoked Potentials in Individuals with Autism Spectrum Disorder. Journal of the American Academy of Audiology. 2021; 32(6): 379-85.

BACKGROUND: Neurological, structural, and behavioral abnormalities are widely reported in individuals with autism spectrum disorder (ASD); yet there are no objective markers to date. We postulated that by using dominant and nondominant ear data, underlying differences in auditory evoked potentials (AEPs) between ASD and control groups can be recognized. PURPOSE: The primary purpose was to identify if significant differences exist in AEPs recorded from dominant and nondominant ear stimulation in (1) children with ASD and their matched controls, (2) adults with ASD and their matched controls, and (3) a combined child and adult ASD group and control group. The secondary purpose was to explore the association between the significant findings of this study with those obtained in our previous study that evaluated the effects of auditory training on AEPs in individuals with ASD. RESEARCH DESIGN: Factorial analysis of variance with interaction was performed. STUDY SAMPLE: Forty subjects with normal hearing between the ages of 9 and 25 years were included. Eleven children and 9 adults with ASD were age- and gender-matched with neurotypical peers. DATA COLLECTION AND ANALYSIS: Auditory brainstem responses (ABRs) and auditory late responses (ALRs) were recorded. Adult and child ASD subjects were compared with non-ASD adult and child control subjects, respectively. The combined child and adult ASD group was compared with the combined child and adult control group. RESULTS: No significant differences in ABR latency or amplitude were observed between ASD and control groups. ALR N1 amplitude in the dominant ear was significantly smaller for the ASD adult group compared with their control group. Combined child and adult data showed significantly smaller amplitude for ALR N1 and longer ALR P2 latency in the dominant ear for the ASD group compared with the control group. In our earlier study, the top predictor of behavioral improvement following auditory training was ALR N1 amplitude in the dominant ear. Correspondingly, the ALR N1 amplitude in the dominant ear yielded group differences in the current study. CONCLUSIONS: ALR peak N1 amplitude is proposed as the most feasible AEP marker in the evaluation of ASD.

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5. Panda PK, Shikha D, Sharawat IK. Association of Autism Spectrum Disorder with Pre-symptomatic Duchenne Muscular Dystrophy: Isolated Elevation of Transaminases as a Diagnostic Clue. Annals of Indian Academy of Neurology. 2021; 24(4): 603-4.

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6. Pellicano E, den Houting J. Annual Research Review: Shifting from ‘normal science’ to neurodiversity in autism science. Journal of child psychology and psychiatry, and allied disciplines. 2022; 63(4): 381-96.

Since its initial description, the concept of autism has been firmly rooted within the conventional medical paradigm of child psychiatry. Increasingly, there have been calls from the autistic community and, more recently, nonautistic researchers, to rethink the way in which autism science is framed and conducted. Neurodiversity, where autism is seen as one form of variation within a diversity of minds, has been proposed as a potential alternative paradigm. In this review, we concentrate on three major challenges to the conventional medical paradigm – an overfocus on deficits, an emphasis on the individual as opposed to their broader context and a narrowness of perspective – each of which necessarily constrains what we can know about autism and how we are able to know it. We then outline the ways in which fundamental elements of the neurodiversity paradigm can potentially help researchers respond to the medical model’s limitations. We conclude by considering the implications of a shift towards the neurodiversity paradigm for autism science.

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7. Rinaldi B, Ge YH, Freri E, Tucci A, Granata T, Estienne M, Sun JH, Gérard B, Bayat A, Efthymiou S, Gervasini C, Shi YS, Houlden H, Marchisio P, Milani D. Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene. Neurogenetics. 2022; 23(1): 27-35.

AMPA-type glutamate receptors (AMPARs) are postsynaptic ionotropic receptors which mediate fast excitatory currents. AMPARs have a heterotetrameric structure, variably composed by the four subunits GluA1-4 which are encoded by genes GRIA1-4. Increasing evidence support the role of pathogenic variants in GRIA1-4 genes as causative for syndromic intellectual disability (ID). We report an Italian pedigree where some male individuals share ID, seizures and facial dysmorphisms. The index subject was referred for severe ID, myoclonic seizures, cerebellar signs and short stature. Whole exome sequencing identified a novel variant in GRIA3, c.2360A > G, p.(Glu787Gly). The GRIA3 gene maps to chromosome Xq25 and the c.2360A > G variant was transmitted by his healthy mother. Subsequent analysis in the family showed a segregation pattern compatible with the causative role of this variant, further supported by preliminary functional insights. We provide a detailed description of the clinical evolution of the index subjects and stress the relevance of myoclonic seizures and cerebellar syndrome as cardinal features of his presentation.

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8. Torres A, Kearney KB, Berlingo L, Brady MP. « What ELSE about this job? » Teaching Job Decision-Making to College Students With Intellectual and Developmental Disabilities. Journal of developmental and physical disabilities. 2021: 1-20.

Decision-making is the central element of self-determination, requiring targeted, systematic instruction to learn. In this study, researchers developed a multicomponent intervention, « What ELSE about this job? », to teach job decision-making skills to college students with intellectual and developmental disabilities. The intervention coupled remote audio coaching (RAC) with a mnemonic device, ‘ELSE’, to guide students to make decisions about whether certain jobs would be a good fit for them. The study aimed to investigate the effectiveness of the intervention and determine whether the skills would maintain once the intervention was removed. All students who received the intervention substantially increased their ability to make job decisions. Additionally, all participants maintained the skills upon removal of the intervention, and showed signs of generalizing their skills to novel job coaches and web-based job search apps. Implications and future research are discussed.

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9. Wang N, Yao D, Ma L, Liu M. Multi-site clustering and nested feature extraction for identifying autism spectrum disorder with resting-state fMRI. Medical image analysis. 2022; 75: 102279.

Brain functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) has been widely employed to study neuropsychiatric disorders such as autism spectrum disorder (ASD). Existing studies usually suffer from (1) significant data heterogeneity caused by different scanners or studied populations in multiple sites, (2) curse of dimensionality caused by millions of voxels in each fMRI scan and a very limited number (tens or hundreds) of training samples, and (3) poor interpretability, which hinders the identification of reproducible disease biomarkers. To this end, we propose a Multi-site Clustering and Nested Feature Extraction (MC-NFE) method for fMRI-based ASD detection. Specifically, we first divide multi-site training data into ASD and healthy control (HC) groups. To model inter-site heterogeneity within each category, we use a similarity-driven multiview linear reconstruction model to learn latent representations and perform subject clustering within each group. We then design a nested singular value decomposition (SVD) method to mitigate inter-site heterogeneity and extract FC features by learning both local cluster-shared features across sites within each category and global category-shared features across ASD and HC groups, followed by a linear support vector machine (SVM) for ASD detection. Experimental results on 609 subjects with rs-fMRI from the ABIDE database with 21 imaging sites suggest that the proposed MC-NFE outperforms several state-of-the-art methods in ASD detection. The most discriminative FCs identified by the MC-NFE are mainly located in default mode network, salience network, and cerebellum region, which could be used as potential biomarkers for fMRI-based ASD analysis.

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10. Whittaker DE, Oleari R, Gregory LC, Le Quesne-Stabej P, Williams HJ, Torpiano JG, Formosa N, Cachia MJ, Field D, Lettieri A, Ocaka LA, Paganoni AJ, Rajabali SH, Riegman KL, De Martini LB, Chaya T, Robinson IC, Furukawa T, Cariboni A, Basson MA, Dattani MT. A recessive PRDM13 mutation results in congenital hypogonadotropic hypogonadism and cerebellar hypoplasia. The Journal of clinical investigation. 2021; 131(24).

The positive regulatory (PR) domain containing 13 (PRDM13) putative chromatin modifier and transcriptional regulator functions downstream of the transcription factor PTF1A, which controls GABAergic fate in the spinal cord and neurogenesis in the hypothalamus. Here, we report a recessive syndrome associated with PRDM13 mutation. Patients exhibited intellectual disability, ataxia with cerebellar hypoplasia, scoliosis, and delayed puberty with congenital hypogonadotropic hypogonadism (CHH). Expression studies revealed Prdm13/PRDM13 transcripts in the developing hypothalamus and cerebellum in mouse and human. An analysis of hypothalamus and cerebellum development in mice homozygous for a Prdm13 mutant allele revealed a significant reduction in the number of Kisspeptin (Kiss1) neurons in the hypothalamus and PAX2+ progenitors emerging from the cerebellar ventricular zone. The latter was accompanied by ectopic expression of the glutamatergic lineage marker TLX3. Prdm13-deficient mice displayed cerebellar hypoplasia and normal gonadal structure, but delayed pubertal onset. Together, these findings identify PRDM13 as a critical regulator of GABAergic cell fate in the cerebellum and of hypothalamic kisspeptin neuron development, providing a mechanistic explanation for the cooccurrence of CHH and cerebellar hypoplasia in this syndrome. To our knowledge, this is the first evidence linking disrupted PRDM13-mediated regulation of Kiss1 neurons to CHH in humans.

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11. Yang K, Shi Y, Du X, Wang J, Zhang Y, Shan S, Yuan Y, Wang R, Zhou C, Liu Y, Cai Z, Wang Y, Fan L, Xu H, Yu J, Cheng J, Li F, Qiu Z. SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice. Cell reports. 2021; 37(5): 109939.

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, causing defects of social interaction and repetitive behaviors. Here, we identify a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene in people with ASD without neurodevelopmental delay. We find that Senp1(+/-) mice exhibit core autistic-like symptoms such as social deficits and repetitive behaviors but normal learning and memory ability. Moreover, we find that inhibitory and excitatory synaptic functions are severely affected in the retrosplenial agranular (RSA) cortex of Senp1(+/-) mice. Lack of Senp1 leads to increased SUMOylation and degradation of fragile X mental retardation protein (FMRP), also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescues the defects of synaptic function and autistic-like symptoms of Senp1(+/-) mice. Together, these results demonstrate that disruption of the SENP1-FMRP regulatory axis in the RSA causes autistic symptoms, providing a candidate region for ASD pathophysiology.

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12. Zhang P, Gao Z, Jia J, Chen Q. [Autism spectrum disorder/development delay in siblings with SCN2A mutations caused by germline mosaicism]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2021; 38(11): 1097-100.

OBJECTIVE: To report on a family which has two siblings with SCN2A mutation caused by germline mosaicism suffering from autism spectrum disorder/development delay (ASD/DD). METHODS: Clinical data was collected for the proband and his parents. Next generation sequencing (NGS) was carried out on the proband and his parents. Suspected mutations were verified by Sanger sequencing of the proband, his parents and brother. To detect whether there is a low proportion of somatic mosaicism in the parents, a droplet digital PCR was conducted. The result of ddPCR showed that the father was germline mosaicism (0.233%). RESULTS: NGS has identified a de novo splicing mutation of the SCN2A gene, c.605+1G>A, in the proband and his brother. Combined with its clinical phenotype and inheritance pattern, SCN2A was judged to be the pathogenic gene. Above findings strongly suggested parental germline mosaicism. CONCLUSION: ASD/DD in siblings with SCN2A mutations caused by germline mosaicism. Paternal mosaicism should be considered as one of the important inheritance patterns for counseling parents with a child carrying SCN2A mutation. The ddPCR can help to reveal very low proportion of germline mosaicism.

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