Dynamic Regulation of brsk2 in the Social and Motor Development of Zebrafish: A Developmental Behavior Analysis.

Both social and motor development play an essential role in an individual's physical, psychological, and social well-being. It is essential to conduct a dynamic analysis at multiple time points during the developmental process as it helps us better understand and evaluate the trajectory and changes in individual development. Recently, some studies found that mutations in the BRSK2 gene may contribute to motor impairments, delays in achieving motor milestones, and deficits in social behavior and communication skills in patients. However, little is known about the dynamic analysis of social and motor development at multiple time points during the development of the brsk2 gene. We generated a novel brsk2-deficient (brsk2ab-/-) zebrafish model through CRISPR/Cas9 editing and conducted comprehensive morphological and neurobehavioral evaluations, including that of locomotor behaviors, social behaviors, and anxiety behaviors from the larval to adult stages of development. Compared to wild-type zebrafish, brsk2ab-/- zebrafish exhibited a catch-up growth pattern of body length and gradually improved locomotor activities during the developmental process. In contrast, multimodal behavior tests showed that the brsk2ab-/- zebrafish displayed escalating social deficiency and anxiety-like behaviors over time. We reported for the first time that the brsk2 gene had dynamic regulatory effects on motor and social development. It helps us understand developmental trends, capture changes, facilitate early interventions, and provide personalized support and development opportunities for individuals.

Behavioral and Sensory Deficits Associated with Dysfunction of GABAergic System in a Novel shank2-Deficient Zebrafish Model.

Hyper-reactivity to sensory inputs is a common and debilitating symptom of autism spectrum disorder (ASD), but the underlying neural abnormalities remain unclear. Two of three patients in our clinical cohort screen harboring de novo SHANK2 mutations also exhibited high sensitivity to visual, auditory, and tactile stimuli, so we examined whether shank2 deficiencies contribute to sensory abnormalities and other ASD-like phenotypes by generating a stable shank2b-deficient zebrafish model (shank2b-/-). The adult shank2b-/- zebrafish demonstrated reduced social preference and kin preference as well as enhanced behavioral stereotypy, while larvae exhibited hyper-sensitivity to auditory noise and abnormal hyperactivity during dark-to-light transitions. This model thus recapitulated the core developmental and behavioral phenotypes of many previous genetic ASD models. Expression levels of γ-aminobutyric acid (GABA) receptor subunit mRNAs and proteins were also reduced in shank2b-/- zebrafish, and these animals exhibited greater sensitivity to drug-induced seizures. Our results suggest that GABAergic dysfunction is a major contributor to the sensory hyper-reactivity in ASD, and they underscore the need for interventions that target sensory-processing disruptions during early neural development to prevent disease progression.

[Short-term persistent symptoms in preschool children with mild/common coronavirus disease 2019 caused by Omicron variant infection after discharge: a follow-up study]. / Omicronå˜å¼‚æ ªæ„ŸæŸ“çš„è½»åž‹/æ™®é€šåž‹æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žå­¦é¾„å‰å„¿ç«¥å‡ºé™¢åŽçŸ­æœŸç›¸å ³æŒç»­ç—‡çŠ¶çš„éšè®¿.

OBJECTIVES: To investigate the persistent symptoms in preschool children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection, and to provide a basis for developing follow-up plans after infection and reducing and preventing related symptoms after infection. METHODS: The children, aged 0-5 years, who had Omicron BA.2 infection and were discharged from the pediatric ward of Shanghai Renji Hospital South Branch from April 13 to May 8, 2022, were enrolled as subjects, and related demographic and clinical data were collected. The children were followed up from the time to SARS-CoV-2 clearance for two consecutive tests with an interval of >24 hours till 4-5 weeks after clearance, and telephone follow-up was performed on the primary caregivers to investigate related persistent symptoms. RESULTS: Among the 103 children who met the inclusion criteria, there were 61 boys and 42 girls, with a median age of 18 months. The primary caregivers who had received two or more doses of COVID-19 vaccine accounted for 64.1% (66/103). Fever (98.1%, 101/103) was the most common symptom in these children, followed by cough/expectoration (63.1%, 65/103), gastrointestinal problems (37.9%, 39/103), loss of appetite (30.1%, 31/103), weakness (27.2%, 28/103), and nasal obstruction/runny nose (16.5%, 17/103). The follow-up at 1 month after discharge reported that 44 children (42.7%) had at least one persistent symptom, including respiratory symptoms in 14 children (13.6%) and gastrointestinal problems in 19 children (18.4%). The children whose primary caregivers received two or more doses of COVID-19 vaccine had a significantly shorter time to SARS-CoV-2 clearance than those whose primary caregivers did not receive or only received one dose of COVID-19 vaccine (P<0.05), while there was no significant difference between the two groups in the proportion of children with at least one persistent symptom (P>0.05). CONCLUSIONS: Nearly half of the preschool children may have related persistent symptoms after SARS-CoV-2 Omicron variant infection, mainly gastrointestinal and respiratory symptoms. Most of the symptoms may be mild, and continuous follow-up is needed to observe their outcomes. Vaccination of COVID-19 vaccine for primary caregivers has a certain protective effect on children.

Prolonged use of nitric oxide donor sodium nitroprusside induces ocular hypertension in mice.

Nitric oxide (NO) donors are promising therapeutic candidates for treating intraocular hypertension (IOP) and glaucoma. This study aims to investigate the effect of prolonged use of NO donor sodium nitroprusside (SNP) on IOP. Since SNP has a short biological half-life, a nanoparticle drug delivery system (mesoporous silica nanoparticles) has been used to deliver SNP to the target tissues (trabecular meshwork and Schlemm's canal). We find that the sustained use of NO donor initially reduced IOP followed, surprisingly, by IOP elevation, which could not recover by drug withdraw but could be reversed by the antioxidant MnTMPyP application. The IOP elevation and normalization coincide with increased and reduced protein nitration in the mouse conventional outflow tissue. These findings suggest that the prolonged use of NO donor SNP may be problematic as it can cause outflow tissue damage by protein nitration. MnTMPyP is protective of the nitrative damage which could be considered to be co-applied with NO donors.

Airborne particulate matter (PM2.5) triggers cornea inflammation and pyroptosis via NLRP3 activation.

Although studies have demonstrated that fine particulate matter (PM2.5) induces ocular surface damage, PM2.5 exposure causes cornea toxicity is not entirely clear. The aim of this study is to investigate the role of the nod-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis in PM2.5-related corneal toxicity. Human corneal epithelial cells (HCECs) were exposed to different concentrations of PM2.5, and the cell viability, expressions of NLRP3 inflammasome mediated pyroptosis axis molecules and intracellular reactive oxygen species (ROS) formation were measured in HCECs. Animal experiments were undertaken to topically apply PM2.5 suspension to mouse eyes for three months and the pyroptosis related molecules in the mouse corneas were measured. RESULTS: Our results showed a dose-dependent decrease of HCEC viability in the PM2.5-treated cells. NLRP3 inflammasome-mediated pyroptosis axis (NLRP3, ASC, GSDMD, caspase-1, IL-1ß, and IL-18) were activated in the PM2.5-treated HCECs, accompanied by increased ROS formation. Further in vivo study confirmed the activation of this pathway in the mouse corneas exposed to PM2.5. In conclusion, this study provids novel evidence that PM2.5 induces corneal toxicity by triggering cell pyroptosis.

Integrative transcriptomics and proteomic analysis of extraocular muscles from patients with thyroid-associated ophthalmopathy.

Our study aimed to reveal the underlying pathologic mechanisms of thyroid-associated ophthalmopathy (TAO) by integrative transcriptomics and proteomic analysis of extraocular muscles (EOM). The study involved 11 TAO patients (clinical activity score ≤ 2) and 11 control donors. Total RNA was extracted from EOM samples of 5 TAO patients and 5 control individuals for gene microarray analysis to reveal differentially expressed genes. Concurrently, EOM samples from 3 TAO patients and 3 control individuals were lysed for quantitative proteomic analysis. Differentially expressed genes and proteins were identified, followed by functional and pathway enrichment analysis and protein-protein interaction network construction. Concordance between proteins and transcripts was examined, and functional annotations were conducted. Expressions of versican (VCAN) and lipocalin 1 (LCN1) in EOM samples from another 3 TAO patients and 3 control individuals were measured by western blotting. In total, 952 genes and 137 proteins were identified as differentially expressed, as well as 96 differentially expressed proteins without significantly changed mRNA abundance. Proteins mainly related to the composition (such as MYH1, MYH2, and MYH13) and contraction force (MYH3, MYH8, ACTN3, and TNNT1) of the muscle fibers were significantly up-regulated in EOM samples of TAO, as well as those (such as VCAN, MPZ, and PTPRC) associated with cell adhesion. In addition, differentially expressed proteins related to the components and metabolism of extracellular matrix (ECM) (such as COL1A1, COL1A2, COL2A1, VCAN, OGN, and DCN) were identified. Similarly, expressions of genes involved in cell adhesion and ECM metabolism were significantly different between EOM samples of TAO patients and controls. Western blotting verified that VCAN involved in ECM proteoglycans and diseases associated with glycosaminoglycan metabolism was markedly higher in EOM samples of TAO, whereas LCN1 was obviously decreased. In conclusion, this study demonstrated the significantly altered cellular components of EOM, muscle contraction, cell adhesion and ECM metabolism, which might be involved in the pathologic mechanisms and/or consequences of TAO.

Detection of County Economic Development Using LJ1-01 Nighttime Light Imagery: A Comparison with NPP-VIIRS Data.

Nighttime light (NTL) remote sensing data have been widely used to derive socioeconomic indicators at the national and regional scales to study regional economic development. However, most previous studies only chose a single measurement indicator (such as GDP) and adopted simple regression methods to investigate the economic development of a certain area based on DMSP-OLS or NPP-VIIRS stable NTL data. The status quo shows the problems of using a single evaluation index-it has a low evaluation precision. The LJ1-01 satellite is the first dedicated NTL remote sensing satellite in the world, launched in July 2018. The data provided by LJ1-01 have a higher spatial resolution and fewer blooming phenomena. In this paper, we compared the accuracy of the LJ1-01 data and NPP-VIIRS data in detecting county-level multidimensional economic development. In three provinces in China, namely, Hubei, Hunan and Jiangxi, 20 socioeconomic parameters were selected from the following five perspectives: economic conditions, people's livelihood, social development, public resources and natural vulnerability. Then, a County-level Economic Index (CEI) was constructed to evaluate the level of multidimensional economic development, with the spatial pattern of the multidimensional economic development also identified across the study area. The present study adopted the random forest (RF) and linear regression (LR) algorithms to establish the regression model individually, and the results were evaluated by cross-validation. The results show that the RF algorithm greatly improves the accuracy of the model compared with the LR algorithm, and thus is suitable for the study of NTL data. In addition, a better determinate coefficient (R2) based on the LJ1-01 data (0.8168) was obtained than that from the NPP-VIIRS data (0.7245) in the RF model, which reflects that the LJ1-01 data offer better potential in the evaluation of socioeconomic parameters and can be used to identify, both accurately and efficiently, multidimensional economic development at the county level.

NSDHL-containing duplication at Xq28 in a male patient with autism spectrum disorder: a case report.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetics plays a key aetiological role. The gene encoding NAD(P)H steroid dehydrogenase-like protein (NSDHL) is expressed in developing cortical neurons and glia, and its mutation may result in intellectual disability or congenital hemidysplasia. CASE PRESENTATION: An 8-year-old boy presented with a 260-kb NSDHL-containing duplication at Xq28 (151,868,909 - 152,129,300) inherited from his mother. His clinical features included defects in social communication and interaction, restricted interests, attention deficit, impulsive behaviour, minor facial anomalies and serum free fatty acid abnormality. CONCLUSION: This is the first report of an ASD patient with a related NSDHL-containing duplication at Xq28. Further studies and case reports are required for genetic research to demonstrate that duplication as well as mutation can cause neurodevelopmental diseases.

Developmental profiling of ASD-related shank3 transcripts and their differential regulation by valproic acid in zebrafish.

SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood. Here, we investigated temporal, spatial, and isoform-specific expression patterns of shank3 during zebrafish development on the basis of previous researches and the differential effects of each shank3 transcript expression after exposure to valproic acid (VPA), an ASD-associated drug. At first, we observed that both shank3a and shank3b were barely expressed at very early ages (before 24 h post-fertilization (hpf)), whereas their expression levels were increased and mainly enriched in the nervous system after 24 hpf. Secondly, all of the six shank3 transcripts gradually increased during the first 7 hpf and then decreased. Subsequently, they exhibited a second increasing peak between 1 month post-fertilization (mpf) and adulthood. Thirdly, VPA treatment affected the isoform-specific expression of zebrafish shank3. In particular, the mRNA expression levels of those isoforms that contain a SAM domain were significantly increased, whereas the mRNA expression level of those which contained an ANK domain but without a SAM domain was decreased. To conclude, our findings support the molecular diversity of shank3 in zebrafish and provide a molecular framework to understand the isoform-specific function of shank3 in zebrafish.

The factors driving industrial integration: A fuzzy set qualitative comparative analysis.

The integration of modern service and advanced manufacturing industries represents deep industrial reform and profound change in quality concepts, mechanisms, and practices. Integrating these two industries is important for achieving high-quality development and is an area of interest for policymakers and academia. This study analyzes the data of 11 regions in 2021 in the Guangdong-Hong Kong-Macao Greater Bay Area using the fuzzy set qualitative comparative analysis method from the configuration perspective. This study explores the effects of multiple factors, such as economic efficiency, technological innovation, and the policy environment, on improving the coupling coordination level of the modern service and advanced manufacturing industries, and analyzes the path selection of industrial integration development. Overall, economic efficiency, technological innovation, and policy environment factors are not necessary conditions for the integration development of the modern service and advanced manufacturing industries. The multiple impacts of economic efficiency, technological innovation, and policy environment form a multi-restructuring path that drives the integration of the two industries. Owing to the economic development level and resource endowment of different regions, the path dictating the degree of integration between the two industries varies by region. From a holistic perspective, all regions should strive to coordinate the multiple conditions of economic efficiency, technological innovation, and policy environment to break through objective constraints such as the government's conditions and external environment based on their own organizational conditions and resource endowments. Additionally, all regions should strengthen exchanges, cooperation, and integration mechanisms and implement complementary development and distinctive development in core cities in the Greater Bay Area. The results clarify the factors affecting industrial convergence in the Greater Bay Area, enriching existing research methods and laying a foundation for a decision-making theory of industrial integration development.

ABCA1 Deletion Does Not Affect Aqueous Humor Outflow Function in Mice.

Background: ATP binding cassette transporter A1 (ABCA1) is a candidate gene within a POAG susceptibility locus by GWAS analysis, and it is involved in IOP modulation via the Cav1/eNOS/NO signaling pathway. We aim to examine the phenotype of ABCA1 deletion in the ABCA1 gene knockout (Abca1-/-) mice. Methods: The anterior segments of Abca1-/- eyes were imaged by slit-lamp microscopy and anterior segment OCT. IOPs were measured by rebound tonometry. By perfusing enucleated eyes at various pressures, the aqueous humor outflow facility was determined. The mRNA expressions of ABCA1, Cav1, and eNOS were measured by RT-qPCR. The protein expressions were analyzed by western blot and immunofluorescence staining. Results: There was no significant difference in the anterior segment morphology of Abca1-/- mice. IOP and aqueous humor outflow facility did not change in Abca1-/- mice compared with wild-type mice. mRNA and protein expressions of ABCA1 were significantly lower in the outflow tissue of Abca1-/- eyes. The expressions of Cav1 and eNOS were both significantly upregulated in the outflow tissue of Abca1-/- eyes. Conclusion: ABCA1 deletion does not affect IOP and aqueous humor outflow function but the Cav1/eNOS/NO pathway is changed in Abca1-/- mice. The function of ABCA1 in aqueous humor outflow still requires further research.

Computational Interpersonal Communication Model for Screening Autistic Toddlers: A Case Study of Response-to-Name.

Interpersonal communication facilitates symptom measures of autistic sociability to enhance clinical decision-making in identifying children with autism spectrum disorder (ASD). Traditional methods are carried out by clinical practitioners with assessment scales, which are subjective to quantify. Recent studies employ engineering technologies to analyze children's behaviors with quantitative indicators, but these methods only generate specific rule-driven indicators that are not adaptable to diverse interaction scenarios. To tackle this issue, we propose a Computational Interpersonal Communication Model (CICM) based on psychological theory to represent dyadic interpersonal communication as a stochastic process, providing a scenario-independent theoretical framework for evaluating autistic sociability. We apply CICM to the response-to-name (RTN) with 48 subjects, including 30 toddlers with ASD and 18 typically developing (TD), and design a joint state transition matrix as quantitative indicators. Paired with machine learning, our proposed CICM-driven indicators achieve consistencies of 98.44% and 83.33% with RTN expert ratings and ASD diagnosis, respectively. Beyond outstanding screening results, we also reveal the interpretability between CICM-driven indicators and expert ratings based on statistical analysis.

Clinical impact and in vitro characterization of ADNP variants in pediatric patients.

BACKGROUND: Helsmoortel-Van der Aa syndrome (HVDAS) is a rare genetic disorder caused by variants in the activity-dependent neuroprotector homeobox (ADNP) gene; hence, it is also called ADNP syndrome. ADNP is a multitasking protein with the function as a transcription factor, playing a critical role in brain development. Furthermore, ADNP variants have been identified as one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability. METHODS: We assembled a cohort of 15 Chinese pediatric patients, identified 13 variants in the coding region of ADNP gene, and evaluated their clinical phenotypes. Additionally, we constructed the corresponding ADNP variants and performed western blotting and immunofluorescence analysis to examine their protein expression and subcellular localization in human HEK293T and SH-SY5Y cells. RESULTS: Our study conducted a thorough characterization of the clinical manifestations in 15 children with ADNP variants, and revealed a broad spectrum of symptoms including global developmental delay, intellectual disability, ASD, facial abnormalities, and other features. In vitro studies were carried out to check the expression of ADNP with identified variants. Two cases presented missense variants, while the remainder exhibited nonsense or frameshift variants, leading to truncated mutants in in vitro overexpression systems. Both overexpressed wildtype ADNP and all the different mutants were found to be confined to the nuclei in HEK293T cells; however, the distinctive pattern of nuclear bodies formed by the wildtype ADNP was either partially or entirely disrupted by the mutant proteins. Moreover, two variants of p.Y719* on the nuclear localization signal (NLS) of ADNP disrupted the nuclear expression pattern, predominantly manifesting in the cytoplasm in SH-SY5Y cells. LIMITATIONS: Our study was limited by a relatively small sample size and the absence of a longitudinal framework to monitor the progression of patient conditions over time. Additionally, we lacked in vivo evidence to further indicate the causal implications of the identified ADNP variants. CONCLUSIONS: Our study reported the first cohort of HVDAS patients in the Chinese population and provided systematic clinical presentations and laboratory examinations. Furthermore, we identified multiple genetic variants and validated them in vitro. Our findings offered valuable insights into the diverse genetic variants associated with HVDAS.

Analyzing dynamic coupling and coordination of modern service and advanced manufacturing industries in Guangdong-Hong Kong-Macao Greater Bay Area.

Integrating the modern service industry with the advanced manufacturing industry is an important way to cultivate a modern industrial system and achieve high-quality development of economy. This study aims to enhance the supporting and leading role of the Greater Bay Area of Guangdong, Hong Kong, and Macao in China's national economic development and opening up by promoting the in-depth integration of these two industries. A new monitoring system is developed to simulate the level of integration of the modern service and advanced manufacturing industries in the Guangdong-Hong Kong-Macao Greater Bay Area. The dynamic comprehensive evaluation model of stock increment was used to simulate the coupling coordination degree of these two industries. Empirical results reveal that the development of these industries has uneven stock and incremental resource advantages, and their development has not been balanced. The coupling coordination degree of these industries in some areas has become maladjusted, while in other areas, it has fluctuated or developed from coordination to disorderly leap-forward. These findings demonstrate that the study methods and results are significant for analyzing industrial integration processes and promoting in-depth integration development in the Guangdong-Hong Kong-Macao Greater Bay Area. In conclusion, building a monitoring system using the dynamic comprehensive evaluation model of stock increment is an effective way to evaluate the level of integration of these two industries and promote their in-depth integration in the Greater Bay Area.

Reduction-responsive polymeric micelles for trans-corneal targeted delivery of microRNA-21-5p and glaucoma-specific gene therapy.

The therapeutic value of microRNA (miRNA) for the treatment of glaucoma has become a focus of attention. However, naked miRNA cannot cross the corneal barrier and reach the target tissue by itself. Thus, the precise transport of miRNA to the target sites is key to the success of gene therapy. Herein, we selected a miRNA, namely miR-21-5p, based on its unique intraocular pressure (IOP) mechano-sensing property. Moreover, a biocompatible polymeric poly(L-lysine) (PLL) micelle conjugated with collagenase and ABCA1 antibody was judiciously constructed to achieve the trans-corneal and target delivery of miR-21-5p to the trabecular meshwork (TM) and Schlemm's canal (SC) tissues inside the eye. The topically administrated PLL micelles as an eye drop successfully crossed the cornea with the help of collagenase and then preferentially accumulated in the target TM/SC tissues under the guidance of the ABCA1 antibody. When endocytosed by TM/SC cells, the PLL micelles could be decomposed in the reductive lysosomal environment to release miR-21-5p for successfully lowering the IOP by activating the miR-21-5p/eNOS/MMP9 signaling axis, which will open new prospects for glaucoma-specific gene therapy.

Corrigendum: The incidence and clinical characteristics of fragile X syndrome in China.

[This corrects the article DOI: 10.3389/fped.2023.1064104.].

Targeted sequencing and clinical strategies in children with autism spectrum disorder: A cohort study.

Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with genetic and clinical heterogeneity. Owing to the advancement of sequencing technologies, an increasing number of ASD-related genes have been reported. We designed a targeted sequencing panel (TSP) for ASD based on next-generation sequencing (NGS) to provide clinical strategies for genetic testing of ASD and its subgroups. Methods: TSP comprised 568 ASD-related genes and analyzed both single nucleotide variations (SNVs) and copy number variations (CNVs). The Autism Diagnostic Observation Schedule (ADOS) and the Griffiths Mental Development Scales (GMDS) were performed with the consent of ASD parents. Additional medical information of the selected cases was recorded. Results: A total of 160 ASD children were enrolled in the cohort (male to female ratio 3.6:1). The total detection yield was 51.3% for TSP (82/160), among which SNVs and CNVs accounted for 45.6% (73/160) and 8.1% (13/160), respectively, with 4 children having both SNVs and CNV variants (2.5%). The detection rate of disease-associated variants in females (71.4%) was significantly higher than that in males (45.6%, p = 0.007). Pathogenic and likely pathogenic variants were detected in 16.9% (27/160) of the cases. SHANK3, KMT2A, and DLGAP2 were the most frequent variants among these patients. Eleven children had de novo SNVs, 2 of whom had de novo ASXL3 variants with mild global developmental delay (DD) and minor dysmorphic facial features besides autistic symptoms. Seventy-one children completed both ADOS and GMDS, of whom 51 had DD/intellectual disability (ID). In this subgroup of ASD children with DD/ID, we found that children with genetic abnormalities had lower language competence than those without positive genetic findings (p = 0.028). There was no correlation between the severity of ASD and positive genetic findings. Conclusion: Our study revealed the potential of TSP, with lower cost and more efficient genetic diagnosis. We recommended that ASD children with DD or ID, especially those with lower language competence, undergo genetic testing. More precise clinical phenotypes may help in the decision-making of patients with genetic testing.

The incidence and clinical characteristics of fragile X syndrome in China.

Introduction: Fragile X syndrome (FXS) is a X-linked neurodevelopmental disorder (NDD). This study aims to investigate the incidence of FXS in Chinese children and analyze the comprehensive clinical characteristics of these FXS children. Methods: Children diagnosed with idiopathic NDD were recruited between 2016 and 2021 from the department of Child Health Care, Children's Hospital of Fudan University. We combined tetraplet-primed PCR-capillary electrophoresis and whole exome sequencing (WES)/panel or array-based comparative genomic hybridization (array-CGH) to identify the size of the CGG repeats and the mutations or copy number variations (CNVs) in the genome and in FMR1. The clinical features of FXS children were analyzed according to pediatricians' recording, parental questionnaires, the results of examinations and follow-up. Results: The incidence of FXS in Chinese children with idiopathic NDD was 2.4% (42/1753) and in those with FXS, 2.38% had a deletion (1/42). Here, we present the clinical characteristics of 36 children with FXS. Overweight was observed in two boys. The average intelligence quotient (IQ)/development quotient (DQ) of all FXS patients was 48. The average ages of meaningful words and walking alone were 2 years and 10 months and 1 year and 7 months, respectively. The most frequent repetitive behavior was stimulated by hyperarousal to sensory stimulation. On social aspects, social withdrawal, social anxiety, and shyness accounted for 75%, 58%, and 56% of the total number of children, respectively. Approximately 60% of FXS children in this cohort were emotionally labile and prone to temper tantrums. Self-injury and aggression toward others could also be observed, at 19% and 28%, respectively. The most frequent behavioral problem was attention-deficit hyperactivity disorder (ADHD) seen in 64% and the most common facial features were a narrow and elongated face and large or prominent ears in 92% of patients. Discussion: Screening of FMR1 full mutation provides the possibility for patients' further medical supports and the clinical features of FXS children obtained in this study will increase the understanding and diagnosis of FXS.

Clinical characterization of Lamb-Shaffer syndrome: a case report and literature review.

BACKGROUND: Lamb-Shaffer syndrome (LAMSHF, MIM 616,803) is a rare neurodevelopmental disorder due to haploinsufficiency of SOX5. Furthermore, studies about the clinical features of LAMSHF patients with same allele of c.1477C > T (p. R493*) are very limited. CASE PRESENTATION: We analyzed the phenotypes of one of our cases and two previously reported cases with c.1477C > T (p. R493*), and reviewed the correlating literature. A de novo heterozygous variation c.1477C > T (p. R493*) in SOX5 was identified in a 4 years and 2 months old boy with global development delay by trio-based whole exome sequencing. We compared our case and previously 2 cases reported with recurrent variation, the overlapping clinical features are global developmental delay or intellectual disability, language delay and scoliosis, but their other clinical characteristics are different. CONCLUSIONS: This study suggests that the clinical features of LAMSHF patients with recurrent variations in the SOX5 gene are different. It is suggested that the LAMSHF-related SOX5 gene should be screened and included as one of the candidate genes for neurodevelopmental disorders of unknown etiology.

A multicenter clinical study on parent-implemented early intervention for children with global developmental delay.

Objective: Early identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future. Methods: During the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed. Results: The average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P < 0.05). Furthermore, there was a significant decrease in the mean standard score of dysfunctional interaction, difficult children and the total level of parental stress in the term test for the experimental groups (P < 0.001 for all). Conclusions: PIEIP intervention can significantly improve the developmental outcome and prognosis of children with GDD, especially in the areas of locomotor, personal-social, and language.