BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

To determine the impact of Cysticercus cellulose (C. cellulose) infection on mental health among school-aged children in Tibetan agricultural areas of Sichuan Province.
 Methods: In October 2015, all primary schools located in Tibetan agricultural areas in Yajiang, Ruoergai, and Muli county of Sichuan Province were selected as the research sites. All school-aged children at five- and six-grade were enrolled for the study by a multistage stratified cluster sampling method. Antibodies against C. cellulose were detected. Mental Health Test and questionnaire survey were conducted for school-aged children to collect data. The impact of C. cellulose infection on mental health among school-aged children was analyzed with the multilevel linear regression.
 Results: A total of 2 453 school-aged children were investigated. The C. cellulose seropositive rate was 6.03% (148/2 453). There were 0.16% (4/2 453) patients with seropositive accompanied by seizure, 2.28% (56/2 453) with seropositive accompanied by headache, 2.08% (51/2 453) with seropositive accompanied by frequent weak, and 0.41% (10/2 453) were seropositive accompanied by frequent nausea. The rate of C. cellulose infection was 4.53% (111/2 453). The mean score of the mental health test was 6.59±2.61. There were significant difference in score of mental health test in children whose demographic characteristics were different. The mental health scores of school-aged children were clustered at the school level. After controlling the factors of demographic characteristics, the result of multilevel model demonstrated that the factor of school-aged children with C. cellulose seropositive accompanied by headache was statistically significant (β=1.14, P=0.017).
 Conclusion: The status of C. cellulose infection among school-aged children in Tibetan agricultural areas is not optimistic. C. cellulose infection has impacted on mental health of local school-aged children. It is necessary to strengthen the prevention and control of C. cellulose infection in epidemic area.
Animals ; Child ; Cysticercosis ; complications ; diagnosis ; epidemiology ; Cysticercus ; Humans ; Mental Health ; Neurodevelopmental Disorders ; epidemiology ; etiology ; Seroepidemiologic Studies ; Tibet ; epidemiology

Chromosome microarray analysis (CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon. We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6% (59 out of 434). This gave a detection rate of 14.7% for developmental delay/intellectual disability (DD/ID, 38/259) and 12% for autism spectrum disorders (ASDs, 21/175). Thirty-three recurrent (n ≥ 2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes (such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes). The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results (94.9%) had benefits, allowing earlier diagnosis (36/59), prioritized full clinical management (28/59), medication changes (7/59), a changed prognosis (30/59), and prenatal genetic counseling (15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential. We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility.
Age Factors ; Child ; Child, Preschool ; China ; epidemiology ; ethnology ; Chromosome Disorders ; genetics ; physiopathology ; Chromosomes ; genetics ; DNA Copy Number Variations ; genetics ; Disease Management ; Female ; Humans ; Infant ; Male ; Microarray Analysis ; methods ; Neurodevelopmental Disorders ; diagnosis ; ethnology ; genetics ; physiopathology

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
Biomarkers/blood* ; Child ; Child Health ; Child, Preschool ; Cohort Studies ; Environmental Exposure/adverse effects* ; Environmental Health ; Environmental Pollutants/adverse effects* ; Female ; Fetal Blood/chemistry* ; Follow-Up Studies ; Growth/drug effects* ; Humans ; Hypersensitivity/etiology* ; Infant ; Japan/epidemiology* ; Male ; Neurodevelopmental Disorders/etiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology* ; Prevalence ; Smoking/adverse effects*