Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective To explore the applicability of four risk assessment methods in evaluating occupational health risks associated with low-level benzene homologues exposure in key work sites within the automobile manufacturing industry. Methods The work sites (paint mixing and spray painting) with exposure to benzene homologues among six automobile manufacturing enterprises in Guangdong Province were selected as the study subjects using the judgmental sampling method. Qualitative risk assessment, exposure index method, non-carcinogenic risk assessment, and the International Council on Mining and Metals risk rating method were independently applied to evaluate the occupational health risks of benzene homologues at these work sites. Accuracy, consistency, and correlation of the four methods were compared. Results The air levels of benzene, toluene, xylene, and ethylbenzene in work sites of paint mixing and spray painting across all six enterprises met national occupational health standards. The median ratios of occupational exposure limits for benzene and toluene in spray painting site were higher than those in paint mixing site (0.017 vs 0.010, P<0.05). Using this ratio as a reference for evaluating method accuracy, the non-carcinogenic risk assessment method could distinguish paint mixing site from spray painting site in terms of risk level (P<0.05), whereas the other three methods could not (both P>0.05). The result of consistency testing revealed that the Kappa coefficients between the four methods ranged from -0.13-0.26, indicating poor consistency. The result of Spearman correlation analysis showed that the non-carcinogenic risk assessment and exposure index methods had higher correlation with occupational exposure limits ratios (Spearman correlation coefficients were 0.501 and 0.656, respectively, all P<0.05). Conclusion Occupational health risk assessment can serve as a supplementary tool to evaluate the hazard level of key work sites in the automobile manufacturing industry. Non-carcinogenic risk assessment shows higher accuracy.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To explore the effects of genotypes of one-carbon metabolism (OCM)-related enzyme single nucleotide polymorphisms (SNPs) sites and anti-epileptic drugs on OCM metabolite levels in epileptic patients, and to screen valproic acid (VPA) teratogenic susceptibility genes.Methods:Three hundred and seventy-two epileptic patients, admitted to our hospital from January 2019 to December 2020, were enrolled in the study; patients taking VPA, levetiracetam (LEV), lamotrigine (LTG) or oxcarbazepine (OXC) for more than 6 months without attack during regular medication were classified as VPA group ( n=95), LEV group ( n=61), LTG group ( n=57) and OXC group ( n=70); firstly diagnosed epileptic patients who had never taken antiepileptic drugs or had not taken antiepileptic drugs in the previous 6 months were assigned into blank control group ( n=89). Plasma folic acid (FA), vitamin B12 (VitB 12) and homocysteine (Hcy) levels were determined by automatic chemiluminescence immunoassay, and genotypes of OCM-related enzyme SNPs sites were detected by Sequenom iPLEX. Results:(1) As compared with LEV group and blank control group, VPA group had significantly decreased FA level and significantly increased Hcy level ( P<0.05). (2) Patients with DNA methyltransferase (DNMT) 3a rs12987326(-178G>A) GA type had significantly higher Hcy level than those with GG type ( P<0.05); patients with DNMT1 rs2288350(82G>C) GC type had significantly higher Hcy level than those with GG type ( P<0.05); patients with DNMT1 rs75616428 (55850G>C) GC type had significantly lower VitB 12 level than those with GG type ( P<0.05). Patients with DNMT1 rs1863771(128G>A) GA+AA type had significantly higher FA level than those with GG type, patients with folate receptor 2 rs2298444(59T>C) CT+CC type had significantly higher Hcy level than those with TT type, patients with 5,10-methylenetetrahydrofolate reductase rs1801131(1298A>C) AC+CC type had significantly higher Hcy level than those with AA type, and patients with DNMT3a rs6722613(2327C>T) CT+TT type had significantly lower VitB 12 level than those with CC type ( P<0.05). Conclusions:Decreased FA and increased Hcy levels can be noted in epileptic patients who used VPA; some gene variations in SNPs of OCM also affect the OCM metabolite levels in epileptic patients. Epileptic patients during pregnancy should avoid using VPA or detecting SNPs genotypes before medication to reduce the incidence of fetal malformation.

OBJECTIVETo provide data for the occupational health supervision by analyzing the occupational health status in manufacturing industry in Guangzhou, China.

METHODSThe occupational health investigation was performed in 280 enterprises randomly selected from 8 industries based on industry stratification. According to the occupational health standards, 198 out of the 280 enterprises were supervised and monitored. Sample testing was performed in 3~5 workplaces where workers were exposed to the highest concentration/intensity of occupational hazard for the longest time. Comparative analyses of the overproof rates of hazard were performed among enterprises, workplaces, and testing items from different industries.

RESULTSThe concentrations of occupational hazard in 42.93% (85/198) of enterprises and 22.96% (200/871) of workplaces were above the limit concentration. The most severe hazards were the noises in shipbuilding and wooden furniture industries and the welding fumes in shipbuilding industry. Less than 30% of enterprises were able to provide occupational health examination and periodic test reports of occupational hazard in workplaces. The rate of the workers with abnormal occupational health examination results and the need for reexamination reached 6.63% (832/12 549), and they were mostly from shipbuilding, wooden furniture, and chemical industries.

CONCLUSIONThe occupational health supervision should be strengthened in enterprises, and hazard from noises and dusts should be selectively controlled or reduced. The publication of relevant data and information of occupational health in enterprises should be promoted to enhance social supervision.

Chemical Industry ; China ; Dust ; Humans ; Interior Design and Furnishings ; Manufacturing Industry ; statistics & numerical data ; Noise, Occupational ; Occupational Exposure ; statistics & numerical data ; Occupational Health ; statistics & numerical data ; Welding ; Workplace

Automobiles ; China ; Humans ; Occupational Exposure ; Risk Assessment