Generation of an induced pluripotent stem cell line GWCMCi006-A from a patient with autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures harboring GRIN1 c.389A > G mutation.

Autosomal dominant neurodevelopmental disorder with or without hyperkinetic movements and seizures (NDHMSD) is a rare neurological disorder characterized by neurodevelopmental disorder and hyperkinetic movement, with or without seizures. Heterozygous mutation in the GRIN1 encoding the subunit 1 of the N-methyl-D-aspartate receptor caused this disorder. We first established an induced pluripotent stem cell (iPSC) line from a male patient with c.389A > G mutation in the GRIN1, via reprogramming with KLF4, SOX2, OCT3/4, and c-MYC. Through identification examination, the iPSCs (GWCMCi006-A) stably expressed pluripotency-associated stem cell markers, maintained a normal karyotype, and showed proliferative potential for three-germ layers differentiation.

Corrigendum: ATP6V0C is associated with febrile seizures and epilepsy with febrile seizures plus.

[This corrects the article DOI: 10.3389/fnmol.2022.889534.].

Untargeted urine metabolomics and machine learning provide potential metabolic signatures in children with autism spectrum disorder.

Background: Complementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML. Methods: Untargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autism. Results: A total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p<0.05). The alterations observed in the phosphatidylinositol and inositol phosphate metabolism pathways were linked to the pathophysiology of autism (p<0.05). Conclusion: Significant urinary metabolites, including prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, exhibit associations with autism. Additionally, the involvement of the phosphatidylinositol and inositol phosphate pathways suggests their potential role in the pathophysiology of autism.

Plasma Amino Acid Profile in Children with Autism Spectrum Disorder in Southern China: Analysis of 110 Cases.

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, γ-Amino-n-butyric acid, glutamine, sarcosine, δ-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism.

Brain magnetic resonance imaging as predictors in pediatric anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: To investigate the associations between brain magnetic resonance imaging (MRI) changes and clinical profiles in children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: Clinical data and brain MRI results of children diagnosed with anti-NMDAR encephalitis in Guangzhou Women and Children's Medical Center from October 2014 to June 2022 were retrospectively studied. RESULTS: A total of 143 children (Male: female 54:89) were enrolled, with a mean onset age of 6.8 years (6.8 ± 3.1). 40.6 % (58/143) of patients had abnormal initial brain MRI. Lesions in temporal lobe (34.5 %, 20/58) and frontal lobe (25.9 %, 15/58) were relatively common. Children with abnormal initial brain MRI were prone to have fever (P = 0.023), dystonia (P = 0.037), positive MOG antibodies (P = 0.015), higher cerebrospinal fluid (CSF) white blood cell count (WBC) (P = 0.019) and to receive rituximab treatment (P = 0.037). There were no significant differences in modified Rankin Scale (mRS) scores before immunotherapy, after immunotherapy and at last follow-up between the normal initial brain MRI group and abnormal group. No initial brain MRI changes were found to be associated with relapses. Brain MRI was reviewed in 72 patients at last follow-up with a median follow-up time of 25.5 months and 48.6 % (35/72) of patients had abnormal brain MRI. The mRS score of the group with normal brain MRI at last follow-up was significantly lower than that of the abnormal group. CONCLUSIONS: About 40.0 % of children with anti-NMDAR encephalitis had abnormal initial brain MRI. Initial brain MRI was associated with certain clinical profiles, but not with relapse and prognosis. Around half of patients had abnormal brain MRI at last follow-up and were prone to have higher mRS score.

Satralizumab as an add-on treatment in refractory pediatric AQP4-antibody-positive neuromyelitis optica spectrum disorder: a case report.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system. Relapse and incomplete recovery from relapse are common in NMOSD. Most patients with NMOSD have IgG to aquaporin-4 (AQP4-IgG). New biological agents for AQP4-IgG-seropositive NMOSD, such as satralizumab, have become available for maintenance therapy. Satralizumab is an anti-interleukin-6 receptor monoclonal antibody. To date, few studies have evaluated satralizumab as an add-on treatment in pediatric NMOSD patients. Here, we report an 11-year-old girl with NMOSD who frequently relapsed under long-term treatment, including oral prednisone, rituximab, mycophenolate mofetil (MMF), and maintenance intravenous immunoglobulin treatment even with B-cell depletion. For the poor treatment response and to improve the efficacy of relapse prevention further, the patient received satralizumab treatment as an add-on therapy to MMF plus oral prednisone, with a dose of 120 mg administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks after that. After initiating satralizumab, the patient remained relapse-free for 14 months at the last follow-up. Satralizumab might be effective and safe as an add-on treatment in refractory pediatric AQP4-IgG-seropositive NMOSD under B-cell depletion.

Levetiracetam may be an unsuitable choice for patients with PRRT2-associated self-limited infantile epilepsy.

INTRODUCTION: Self-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve seizures in patients with SeLIE, but the efficacy of levetiracetam has not been investigated. OBJECTIVE: This study aimed to investigate the efficacy of levetiracetam in the treatment of SeLIE patients with PRRT2 mutations. METHODS: The clinical data of 39 SeLIE patients (21 males and 18 females, aged 4.79 ± 1.60 months) with pathogenic variants in PRRT2 or 16p11.2 microdeletion were retrospectively analyzed. Based on the use of initial antiseizure medication (ASM), the patients were classified into two groups: Levetiracetam group (LEG) and Other ASMs group (OAG). The difference of efficacy between the two groups was compared. RESULTS: Among the 39 SeLIE patients, 16 were LEG (10 males and 6 females, aged 5.25 ± 2.07 months), with whom two obtained a seizure-free status (12.50%) and 14 ineffective or even deteriorated (87.50%). Among the 14 ineffective or deteriorated cases, 13 were seizure-controlled after replacing levetiracetam with other ASMs including topiramate, oxcarbazepine, lamotrigine, and valproate, and the remaining one finally achieved remission at age 3. Of the 39 patients, 23 were OAG (11 males and 12 females; aged 4.48 ± 1.12 months), of whom 22 achieved seizure remission, except for one patient who was ineffective with topiramate initially and relieved by oxcarbazepine instead. Although there were no significant differences in gender and age of onset between the two groups, the effective rate was significantly different (12.50% in LEG vs. 95.65% in OAG) (P < 0.01). CONCLUSION: The findings showed that patients with SeLIE caused by the PRRT2 mutations did not benefit from the use of levetiracetam, but could benefit from other ASMs.

Autistic clinical profiles, age at first concern, and diagnosis among children with autism spectrum disorder.

Background: To explore the relationship between autistic clinical profiles and age at first concern and diagnosis among children with autism spectrum disorder. The clinical profiles included the severity of autism, cognition, adaptability, language development, and regression. Methods: The multivariate linear regression model was used to examine the association of diagnostic age and first-concern age with autistic clinical profiles and with further stratification analysis. Results: A total of 801 autistic children were included. Language delay and regression were associated with earlier diagnostic age (language delay: crudeß: -0.80, 95%CI%: -0.92--0.68; regression: crudeß: -0.21, 95%CI%: -0.43--0.00) and the age of first concern of autistic children (language delay: crudeß: -0.55, 95%CI%: -0.65--0.45; regression: crudeß: -0.17, 95%CI%: -0.34--0.00). After stratification by sex, language delay tended to be more associated with the earlier diagnostic age among boys (crudeß: -0.85, 95%CI%: -0.98--0.72) than among girls (crudeß: -0.46, 95%CI%: -0.77--0.16). After stratification by maternal education level or family income level, language delay was most associated with the earlier diagnostic age in autistic children from families with higher socioeconomic levels. Conclusion: Language delay, rather than other symptoms, promoted an earlier diagnostic age. Among male autistic children or children from families with higher socioeconomic levels, language delay was most significantly associated with an earlier age of diagnosis. Cognitive delay, or adaptive delay, was associated with a later age at diagnosis and presented only in autistic children from families with lower socioeconomic levels. There may be sex or socioeconomic inequality in the diagnostic age for autistic children. More publicity and public education about the diversity of autistic symptoms are urgently needed in the future, especially for low-socioeconomic families.

A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a strong genetic liability. Despite extensive studies, however, the underlying pathogenic mechanism still remains elusive. In the present study, we identified a homozygous mutation in the intron 1 of Wnt1 via large-scale screening of ASD risk/causative genes and verified that this mutation created a new splicing donor site in the intron 1, and consequently, a decrease of WNT1 expression. Interestingly, humanized rat models harboring this mutation exhibited robust ASD-like behaviors including impaired ultrasonic vocalization (USV), decreased social interactions, and restricted and repetitive behaviors. Moreover, in the substantia nigra compacta (SNpc) and the ventral tegmental area (VTA) of mutant rats, dopaminergic (DAergic) neurons were dramatically lost, together with a comparable decrease in striatal DAergic fibers. Furthermore, using single-cell RNA sequencing, we demonstrated that the decreased DAergic neurons in these midbrain areas might attribute to a shift of the boundary of the local pool of progenitor cells from the hypothalamic floor plate to the midbrain floor plate during the early embryonic stage. Moreover, treatments of mutant rats with levodopa could attenuate the impaired USV and social interactions almost completely, but not the restricted and repetitive behaviors. Our results for the first time documented that the developmental loss of DAergic neurons in the midbrain underlies the pathogenesis of ASD, and that the abnormal progenitor cell patterning is a cellular underpinning for this developmental DAergic neuronal loss. Importantly, the effective dopamine therapy suggests a translational significance in the treatment of ASD.

[Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring]. / æ¯äº²å¦Šå¨ ç³–å°¿ç— ä¸Žå­ä»£å­¤ç‹¬ç—‡è°±ç³»éšœç¢å‘ç”Ÿé£Žé™©çš„å ³è”åˆ†æž.

OBJECTIVES: To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring. METHODS: A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored. RESULTS: The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027). CONCLUSIONS: Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.

Pediatric myelin oligodendrocyte glycoprotein antibody-associated disease in southern China: analysis of 93 cases.

Objective: To study the clinical features of children diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in southern China. Methods: Clinical data of children diagnosed with MOGAD from April 2014 to September 2021 were analyzed. Results: A total of 93 children (M/F=45/48; median onset age=6.0 y) with MOGAD were involved. Seizures or limb paralysis was the most common onset or course symptom, respectively. The most common lesion locations in brain MRI, orbital MRI, and spinal cord MRI were basal ganglia and subcortical white matter, the orbital segment of the optic nerve, and the cervical segment, respectively. ADEM (58.10%) was the most common clinical phenotype. The relapse rate was 24.7%. Compared with the patients without relapse, relapsed patients had a longer interval from onset to diagnosis (median: 19 days VS 20 days) and higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer positively persistent (median: 3 months VS 24 months). All patients received IVMP plus IVIG at the acute phase, and 96.8% of patients achieved remission after one to three courses of treatment. MMF, monthly IVIG, and maintaining a low dose of oral prednisone were used alone or in combination as maintenance immunotherapy for relapsed patients and effectively reduced relapse. It transpired 41.9% of patients had neurological sequelae, with movement disorder being the most common. Compared with patients without sequelae, patients with sequelae had higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer persistence (median: 3 months VS 6 months) and higher disease relapse rate (14.8% VS 38.5%). Conclusions: Results showed the following about pediatric MOGAD in southern China: the median onset age was 6.0 years, with no obvious sex distribution difference; seizure or limb paralysis, respectively, are the most common onset or course symptom; the lesions of basal ganglia, subcortical white matter, the orbital segment of the optic nerve, and cervical segment were commonly involved in the CNS MRI; ADEM was the most common clinical phenotype; most had a good response to immunotherapy; although the relapse rate was relatively high, MMF, monthly IVIG and a low dose of oral prednisone might effectively reduce relapse; neurological sequelae were common, and possibly associated with MOG antibody status and disease relapse.

De novo mutations within metabolism networks of amino acid/protein/energy in Chinese autistic children with intellectual disability.

BACKGROUND: Autism spectrum disorder (ASD) is often accompanied by intellectual disability (ID). Despite extensive studies, however, the genetic basis for this comorbidity is still not clear. In this study, we tried to develop an analyzing pipeline for de novo mutations and possible pathways related to ID phenotype in ASD. Whole-exome sequencing (WES) was performed to screen de novo mutations and candidate genes in 79 ASD children together with their parents (trios). The de novo altering genes and relative pathways which were associated with ID phenotype were analyzed. The connection nodes (genes) of above pathways were selected, and the diagnostic value of these selected genes for ID phenotype in the study population was also evaluated. RESULTS: We identified 89 de novo mutant genes, of which 34 genes were previously reported to be associated with ASD, including double hits in the EGF repeats of NOTCH1 gene (p.V999M and p.S1027L). Interestingly, of these 34 genes, 22 may directly affect intelligence quotient (IQ). Further analyses revealed that these IQ-related genes were enriched in protein synthesis, energy metabolism, and amino acid metabolism, and at least 9 genes (CACNA1A, ALG9, PALM2, MGAT4A, PCK2, PLEKHA1, PSME3, ADI1, and TLE3) were involved in all these three pathways. Seven patients who harbored these gene mutations showed a high prevalence of a low IQ score (< 70), a non-verbal language, and an early diagnostic age (< 4 years). Furthermore, our panel of these 9 genes reached a 10.2% diagnostic rate (5/49) in early diagnostic patients with a low IQ score and also reached a 10% diagnostic yield in those with both a low IQ score and non-verbal language (4/40). CONCLUSION: We found some new genetic disposition for ASD accompanied with intellectual disability in this study. Our results may be helpful for etiologic research and early diagnoses of intellectual disability in ASD. Larger population studies and further mechanism studies are warranted.

Assessing the causal association between human blood metabolites and the risk of epilepsy.

BACKGROUND: Metabolic disturbance has been reported in patients with epilepsy. Still, the evidence about the causal role of metabolites in facilitating or preventing epilepsy is lacking. Systematically investigating the causality between blood metabolites and epilepsy would help provide novel targets for epilepsy screening and prevention. METHODS: We conducted two-sample Mendelian randomization (MR) analysis. Data for 486 human blood metabolites came from a genome-wide association study (GWAS) comprising 7824 participants. GWAS data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium for primary analysis and the FinnGen consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: 482 out of 486 metabolites were included for MR analysis following rigorous genetic variants selection. After IVW and sensitivity analysis filtration, six metabolites with causal effects on epilepsy were identified from the ILAE consortium. Only four metabolites remained significant associations with epilepsy when combined with the FinnGen consortium [uridine: odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.48-3.71, P = 0.0003; 2-hydroxystearate: OR = 1.61, 95% CI = 1.19-2.18, P = 0.002; decanoylcarnitine: OR = 0.82, 95% CI = 0.72-0.94, P = 0.004; myo-inositol: OR = 0.77, 95% CI = 0.62-0.96, P = 0.02]. CONCLUSION: The evidence that the four metabolites mentioned above are associated with epilepsy in a causal way provides a novel insight into the underlying mechanisms of epilepsy by integrating genomics with metabolism, and has an implication for epilepsy screening and prevention.

Optimization of Ultrasonic Welding Process Parameters to Enhance Weld Strength of 3C Power Cases Using a Design of Experiments Approach.

Ultrasonic welding (UW) is a joining of plastics through the use of heat generated from high-frequency mechanical motion, which is known as an efficient process in many applications, such as textile, packaging, or automotive. UW of thermoplastics has been widely employed in industry since no polymer degradations are found after UW. However, the trial-and-error approach is frequently used to study optimum UW process parameters for new 3C plastic power cases in current industry, resulting in random efforts, wasted time, or energy consumption. In this study, Taguchi methods are used to study optimum UW process parameters for obtaining high weld strength of a plastic power case. The most important control factor influencing the weld strength is amplitude, followed by weld pressure, hold time, and trigger position. The optimum UW process parameters are amplitude of 43.4 µm, weld pressure of 115 kPa, hold time of 0.4 s, and trigger position of 69.95 mm. Finally, the confirmation experiments are performed to verify the optimum process parameters obtained in this study.

ATP6V0C Is Associated With Febrile Seizures and Epilepsy With Febrile Seizures Plus.

Purpose: To identify novel genetic causes of febrile seizures (FS) and epilepsy with febrile seizures plus (EFS+). Methods: We performed whole-exome sequencing in a cohort of 32 families, in which at least two individuals were affected by FS or EFS+. The probands, their parents, and available family members were recruited to ascertain whether the genetic variants were co-segregation. Genes with repetitively identified variants with segregations were selected for further studies to define the gene-disease association. Results: We identified two heterozygous ATP6V0C mutations (c.64G > A/p.Ala22Thr and c.361_373del/p.Thr121Profs*7) in two unrelated families with six individuals affected by FS or EFS+. The missense mutation was located in the proteolipid c-ring that cooperated with a-subunit forming the hemichannel for proton transferring. It also affected the hydrogen bonds with surround residues and the protein stability, implying a damaging effect. The frameshift mutation resulted in a loss of function by yielding a premature termination of 28 residues at the C-terminus of the protein. The frequencies of ATP6V0C mutations identified in this cohort were significantly higher than that in the control populations. All the six affected individuals suffered from their first FS at the age of 7-8 months. The two probands later manifested afebrile seizures including myoclonic seizures that responded well to lamotrigine. They all displayed favorable outcomes without intellectual or developmental abnormalities, although afebrile seizures or frequent seizures occurred. Conclusion: This study suggests that ATP6V0C is potentially a candidate pathogenic gene of FS and EFS+. Screening for ATP6V0C mutations would help differentiating patients with Dravet syndrome caused by SCN1A mutations, which presented similar clinical manifestation but different responses to antiepileptic treatment.

BMS-470539 Attenuates Oxidative Stress and Neuronal Apoptosis via MC1R/cAMP/PKA/Nurr1 Signaling Pathway in a Neonatal Hypoxic-Ischemic Rat Model.

Neuronal apoptosis induced by oxidative stress plays an important role in the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). Previous studies reported that activation of melanocortin-1 receptor (MC1R) exerts antioxidative stress, antiapoptotic, and neuroprotective effects in various neurological diseases. However, whether MC1R activation can attenuate oxidative stress and neuronal apoptosis after hypoxic-ischemic- (HI-) induced brain injury remains unknown. Herein, we have investigated the role of MC1R activation with BMS-470539 in attenuating oxidative stress and neuronal apoptosis induced by HI and the underlying mechanisms. 159 ten-day-old unsexed Sprague-Dawley rat pups were used. HI was induced by right common carotid artery ligation followed by 2.5 h of hypoxia. The novel-selective MC1R agonist BMS-470539 was administered intranasally at 1 h after HI induction. MC1R CRISPR KO plasmid and Nurr1 CRISPR KO plasmid were administered intracerebroventricularly at 48 h before HI induction. Percent brain infarct area, short-term neurobehavioral tests, Western blot, immunofluorescence staining, Fluoro-Jade C staining, and MitoSox Staining were performed. We found that the expression of MC1R and Nurr1 increased, peaking at 48 h post-HI. MC1R and Nurr1 were expressed on neurons at 48 h post-HI. BMS-470539 administration significantly attenuated short-term neurological deficits and infarct area, accompanied by a reduction in cleaved caspase-3-positive neurons at 48 h post-HI. Moreover, BMS-470539 administration significantly upregulated the expression of MC1R, cAMP, p-PKA, Nurr1, HO-1, and Bcl-2. However, it downregulated the expression of 4-HNE and Bax, as well as reduced FJC-positive cells, MitoSox-positive cells, and 8-OHdG-positive cells at 48 h post-HI. MC1R CRISPR and Nurr1 CRISPR abolished the antioxidative stress, antiapoptotic, and neuroprotective effects of BMS-470539. In conclusion, our findings demonstrated that BMS-470539 administration attenuated oxidative stress and neuronal apoptosis and improved neurological deficits in a neonatal HI rat model, partially via the MC1R/cAMP/PKA/Nurr1 signaling pathway. Early administration of BMS-470539 may be a novel therapeutic strategy for infants with HIE.

Generation of an induced pluripotent stem cell line (GWCMCi005-A) from a patient with Lennox-Gastaut syndrome carrying TANC2 Gln1441Ter mutation.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy, which may arise from genetic etiologies. TANC2 mutation may cause the neurodevelopmental disorders and epilepsy such as LGS. By reprogramming with SOX2, KLF4, c-MYC and OCT3/4, we generated an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) collected from a two-year-old Chinese boy individual to be used as a disease model with TANC2 mutation. By fully examination, the resulting iPSCs expressed pluripotency-associated stem cell markers, maintained the normal karyotype and proliferative potential for three-germ layer differentiation.

Prevalence of epilepsy in autism spectrum disorders: A systematic review and meta-analysis.

LAY ABSTRACT: Autistic individuals experience higher co-occurring medical conditions than the general population, and yet the estimates of autistic individuals with epilepsy are not updated. Co-occurrence of epilepsy in autistic individuals often aggravated cognitive impairment and increased the risk of poor long-term prognosis. Thus, an updated systematic review and meta-analysis was conducted to study the relevant articles published from inception to 2020, evaluate the prevalence of epilepsy in autistic individuals, and further explore the putative factors influencing the prevalence. A total of 66 studies from 53 articles were included in this study. The results showed that epilepsy is more common in autistic individuals than in the general population. The prevalence of epilepsy in autistic individuals in the clinical sample-based studies was higher than that in the population-based based cross-sectional or cohort studies. The prevalence of epilepsy in autistic adults was higher than that in autistic children. A significantly increased prevalence of epilepsy was detected in the autistic adolescent group (11-17 years old), and a higher trend of prevalence of epilepsy was observed in the autistic pre-school group (⩽ 6 -years-old) than that of the autistic school-aged group (7-10 years-old). The prevalence of epilepsy increased with age, female rate, and low intellectual function rate of autistic individuals. However, the human development index of countries was negatively associated with the pooled prevalence, which could be attributed to the different levels of awareness, diagnostic technologies, and autism-service support worldwide. About 1/10 autistic individuals also had epilepsy, which was common in the clinical setting, adolescents, adults, females, or patients with intellectual disability and less common in the country with high human development index. Thus, these findings provided critical and innovative views on the prevalence of epilepsy in autistic individuals and contributed to the targeted clinical management and preventive measures.

Prenatal Folic Acid Supplements and Offspring's Autism Spectrum Disorder: A Meta-analysis and Meta-regression.

We systematically reviewed the evidence on the association between maternal folic acid supplementation and the risk of offspring's autism spectrum disorders (ASD). A total of 10 studies with 23 sub-studies (9795 ASD cases) were included. Folic acid supplementation during early pregnancy was associated with a lower risk of offspring's ASD [OR 0.57, 95% CI 0.41-0.78]. The consumption of a daily amount of at least 400 µg folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD [OR 0.55, 95% CI 0.36-0.83]. Critical effective maternal folic acid supplementation strategies, such as intake timing and intake dosage, may aid the reduction in the risk of offspring ASD. This meta-analysis provided new insights for the prevention of offspring's ASD.