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Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder in which genetics play a major role. Molecular diagnosis may lead to a more accurate prognosis, improved clinical management, and potential treatment of the condition. Both copy number variations (CNVs) and single nucleotide variations (SNVs) have been reported to contribute to the genetic etiology of ASD. The effectiveness and validity of clinical targeted panel sequencing (CTPS) designed to analyze both CNVs and SNVs can be evaluated in different ASD cohorts. CTPS was performed on 573 patients with the diagnosis of ASD. Medical records of positive CTPS cases were further reviewed and analyzed. Additional medical examinations were performed for a group of selective cases. Positive molecular findings were confirmed by orthogonal methods. The overall positive rate was 19.16% (109/569) in our cohort. About 13.89% (79/569) and 4.40% (25/569) of cases had SNVs only and CNVs only findings, respectively, while 0.9% (5/569) of cases had both SNV and CNV findings. For cases with SNVs findings, the SHANK3 gene has the greatest number of reportable variants, followed by gene MYT1L. Patients with MYT1L variants share common and specific clinical characteristics. We found a child with compound heterozygous SLC26A4 variants had an enlarged vestibular aqueduct syndrome and autistic phenotype. Our results showed that CTPS is an effective molecular diagnostic tool for ASD. Thorough clinical and genetic evaluation of ASD can lead to more accurate diagnosis and better management of the condition. [ABSTRACT FROM AUTHOR]

Objective: Early screening contributes to the early detection of children with autism spectrum disorder (ASD). We conducted a longitudinal ASD screening study in a large community setting. The study was designed to investigate the diagnostic rate of ASD screening and determine the effectiveness of ASD screening model in a community-based sample. Methods: We enrolled children who attended 18- and 24-month well-child care visits in Shanghai Xuhui District. Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) and Binomial Observation Test (BOT) were selected as screening instruments. Screen-positive children were referred to a tertiary diagnostic center for comprehensive ASD diagnostic evaluation. Screen-negative children received well-child checkups and follow-up every 3–6 months until age three and were referred if they were suspected of having ASD. Results: A total of 11,190 toddlers were screened, and 36 screen-positive toddlers were diagnosed with ASD. The mean age at diagnosis for these children was 23.1 ± 4.55 months, diagnosed 20 months earlier than ASD children not screened. The diagnostic rate of ASD was 0.32% (95% CI: 0.23–0.45%) in this community-based sample. In addition, 12 screen-negative children were diagnosed with ASD during subsequent well-child visit and follow-up. The average diagnostic rate of ASD rose to 0.43% (95% CI: 0.32–0.57%) when toddlers were followed up to 3 years old. The positive predictive values (PPVs) of M-CHAT-R/F, M-CHAT-R high risk, and BOT for ASD were 0.31, 0.43, and 0.38 respectively. Conclusion: Our findings provide reliable data for estimating the rate of ASD detection and identifying the validity of community-based screening model. M-CHAT-R/F combined with BOT can be an effective tool for early detection of ASD. This community-based screening model is worth replicating. [ABSTRACT FROM AUTHOR]

SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3)-caused autism spectrum disorder (ASD) may present a unique opportunity to clarify the heterogeneous neuropathological mechanisms of ASD. However, the specificity and commonality of disrupted large-scale brain organization in SHANK3- deficient children remain largely unknown. The present study combined genetic tests, neurobehavioral evaluations, and magnetic resonance imaging, aiming to explore the disruptions of both local and networked cortical structural organization in ASD children with and without SHANK3 deficiency. Multiple surface morphological parameters such as cortical thickness (CT) and sulcus depth were estimated, and the graph theory was adopted to characterize the topological properties of structural covariance networks (SCNs). Finally, a correlation analysis between the alterations in brain morphological features and the neurobehavioral evaluations was performed. Compared with typically developed children, increased CT and reduced nodal degree were found in both ASD children with and without SHANK3 defects mainly in the lateral temporal cortex, prefrontal cortex (PFC), temporo-parietal junction (TPJ), superior temporal gyrus (STG), and limbic/paralimbic regions. Besides commonality, our findings showed some distinct abnormalities in ASD children with SHANK3 defects compared to those without. Locally, more changes in the STG and orbitofrontal cortex were exhibited in ASD children with SHANK3 defects, while more changes in the TPJ and inferior parietal lobe (IPL) in those without SHANK3 defects were observed. For the SCNs, a trend toward regular network topology was observed in ASD children with SHANK3 defects, but not in those without. In addition, ASD children with SHANK3 defects showed more alterations of nodal degrees in the anterior and posterior cingulate cortices and right insular, while there were more disruptions in the sensorimotor areas and the left insular and dorsomedial PFC in ASD without SHANK3 defects. Our findings indicate dissociable disruptions of local and networked brain morphological features in ASD children with and without SHANK3 deficiency. Moreover, this monogenic study may provide a valuable path for parsing the heterogeneity of brain disturbances in ASD. [ABSTRACT FROM AUTHOR]