Cohen syndrome combined with psychiatric symptoms: a case report.

BACKGROUND: Cohen syndrome (CS) is a rare autosomal recessive inherited condition characterized by pathological changes affecting multiple systems. The extensive clinical variability associated with CS poses a significant diagnostic challenge. Additionally, there is limited documentation on the co-occurrence of CS with psychiatric symptoms. CASE REPORT: We report a case of a 30-year-old patient exhibiting characteristic physical features and psychiatric symptoms. Whole exome sequencing identified two heterozygous variants, a nonsense variation c.4336 C > T and a missense mutation c.4729G > A. Integrating clinical manifestations with genetic test results, we established the diagnosis of CS combined with psychiatric symptoms. CONCLUSIONS: This case introduces a novel missense variant as a candidate in the expanding array of VPS13B pathogenic variants. Its clinical significance remains unknown, and further investigation may broaden the spectrum of pathogenic variants associated with the VPS13B gene. Early diagnosis of CS is crucial for the prognosis of young children and holds significant importance for their families.

Development and validation of a risk score model for predicting autism based on pre- and perinatal factors.

Background: The use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism. Methods: A stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort. Results: Five factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism. Conclusion: This risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application.

Association between history of miscarriage and autism spectrum disorder.

This case-control study was designed to examine the association between different types of miscarriage history and autism spectrum disorder (ASD), and determine whether the number of miscarriage history affects the risk of ASD. All of 2274 children with ASD and 1086 healthy controls were recruited. Sociodemographic and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Multivariable logistic regression analyses were applied to investigate association between miscarriage history and ASD. Stratified analyses based on sex and types of miscarriages were similarly performed. History of miscarriage was potential risk factors for ASD ([aOR] = 2.919; 95% [CI] = 2.327-3.517). Stratified analyses revealed that induced ([aOR] = 2.763, 95% [CI] = 2.259-3.379) and spontaneous miscarriage history ([aOR] = 3.341, 95% [CI] = 1.939-4.820) were associated with high risk of ASD, respectively. A sex-biased ratio in the risk of ASD was observed between females ([aOR] = 3.049, 95% [CI] = 2.153-4.137) and males ([aOR] = 2.538, 95% [CI] = 1.978-3.251). Stratified analysis of induced miscarriage history revealed that only iatrogenic miscarriage history was associated with an increased risk ASD ([aOR] = 2.843, 95% [CI] = 1.534-4.268). Also, multiple spontaneous miscarriage histories ([aOR] = 1.836, 95% [CI] = 1.252-2.693) were associated with higher autism risk than one spontaneous miscarriages history ([aOR] = 3.016, 95% [CI] = 1.894-4.174). In conclusion, miscarriage history is related to an increased risk for ASD in offspring, which is affected by the types of miscarriage and sex of the fetus.

Peripheral non-enzymatic antioxidants as biomarkers for mood disorders: Evidence from a machine learning prediction model.

Background: Oxidative stress is related to the pathogenesis of mood disorders, and the level of oxidative stress may differ between bipolar disorder (BD) and major depressive disorder (MDD). This study aimed to detect the differences in non-enzymatic antioxidant levels between BD and MDD and assess the predictive values of non-enzymatic antioxidants in mood disorders by applying a machine learning model. Methods: Peripheral uric acid (UA), albumin (ALB), and total bilirubin (TBIL) were measured in 1,188 participants (discover cohort: 157 with BD and 544 with MDD; validation cohort: 119 with BD and 95 with MDD; 273 healthy controls). An extreme gradient boosting (XGBoost) model and a logistic regression model were used to assess the predictive effect. Results: All three indices differed between patients with mood disorders and healthy controls; in addition, the levels of UA in patients with BD were higher than those of patients with MDD. After treatment, UA levels increased in the MDD group, while they decreased in the BD group. Finally, we entered age, sex, UA, ALB, and TBIL into the XGBoost model. The area under the curve (AUC) of the XGBoost model for distinguishing between BD and MDD reached 0.849 (accuracy = 0.808, 95% CI = 0.719-0.878) and for distinguishing between BD with depression episode (BD-D) and MDD was 0.899 (accuracy = 0.891, 95% CI = 0.856-0.919). The models were validated in the validation cohort. The most important feature distinguishing between BD and MDD was UA. Conclusion: Peripheral non-enzymatic antioxidants, especially the UA, might be a potential biomarker capable of distinguishing between BD and MDD.

Individuals with Bipolar Disorder Have a Higher Level of Homocysteine Than Major Depressive Disorder: A Retrospective Chart Review and Observational Study.

Purpose: Previous studies suggest that homocysteine (Hcy) may be involved in the pathogenesis of bipolar disorder (BD) and major depressive disorder (MDD) by influencing glutamatergic transmission, inflammation, and other mechanisms. There are no established biomarkers to distinguish BD from MDD. This study aims to compare Hcy levels between BD and MDD. Patients and Methods: We collected medical records of patients aged 14-75 admitted to the hospital from January 1 to July 1, 2022 with a discharge diagnosis of MDD or BD, including all examinations of patients at admission (acute phase) and discharge (non-acute phase). We measured Hcy levels in healthy controls (HC). Results: The analysis included 104 patients with MDD, 103 patients with BD, and 80 HC. Hcy levels were higher in the MDD and BD group than in the HC group and higher in the BD group than in the MDD group, both in the acute and non-acute phases (all P < 0.05). There was no significant difference in Hcy levels between the psychotropic medication users and non-users in the BD or MDD group (all P > 0.05). Multivariate logistic regression analysis only for the MDD and BD group indicated that the likelihood of BD diagnosis was significantly associated with Hcy levels (in the acute phase: OR = 1.052, P = 0.016; in the non-acute phase: OR = 1.101, P < 0.001) after controlling for gender, age, and metabolic indicators. Conclusion: Our study suggests that Hcy levels were elevated in MDD and BD patients and were higher in BD patients than in MDD patients, which provides evidence for a possible relationship between one-carbon metabolism and the pathogenesis of BD. Besides, Hcy may be one of the potential biomarkers to distinguish BD from MDD.

Individuals with bipolar disorder have a higher level of uric acid than major depressive disorder: a case-control study.

At present, no well-established biomarkers were ever found to distinguish unipolar depression and bipolar disorder (BD). This study aimed to provide a clearer comparison of UA levels between BD and major depressive disorder. Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences in UA levels of BD-M (bipolar mania/hypomania) were higher than BD-D (bipolar depression) subgroups, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. The comparison of number of participants with hyperuricemia among groups confirmed the above results. There were no significant differences in UA levels of between drug-use and drug-free/naïve subgroups. UA could distinguish BD and UD significantly both in acute and remission stage. The study suggests patients with BD had a higher level of UA than UD, especially in mania episode. UA may be a potential biomarker to distinguish BD from UD.

Neurocognition Function of Patients With Bipolar Depression, Unipolar Depression, and Depression With Bipolarity.

Much evidence shows that some Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)-defined unipolar depression (UD) with bipolarity manifests bipolar diathesis. Little is known about the cognitive profiles of patients with depression with bipolarity (DWB). The study aimed to investigate the differences in cognitive profiles among patients with bipolar depression (BD), major depressive disorder (namely, UD), and DWB. Drug-naïve patients with BD, UD, and DWB and healthy controls (HC) were recruited (30 cases in each group). Cognitive function was evaluated by THINC-it (THINC-intelligent tool), Wisconsin Card Sorting Test (WCST), and continuous performance test (CPT). For THINC-it, no significant differences of the Z-scores in both objective and subjective factors were found between the DWB group and BD group, but the Z-scores in the BD group were significantly lower than those in the UD group. For WCST, significant differences were found between the BD group and DWB group in the number of responses, categories completed, trails to completed first category, perseverative responses, and perseverative errors. All the indices of WCST in the DWB group were significantly worse than those in the UD group except for trails to completed first category and total number of response correct. For CPT, only scores of leakage responses and false responses in the four-digit number in the BD group and DWB group were significantly higher than those in the UD group; no significant difference was found between the BD group and DWB group. The results indicated that patients with DWB might perform differently from those with UD but similarly to those with BD with cognition impairment.

Pathological gambling in a patient on piribedil: A case report.

RATIONALE: Piribedil is an orally active dopamine agonist that has been widely used for Parkinson disease (PD), with its partial D2/D3 agonistic functions and alpha2-adrenoreceptor antagonistic effects, piribedil has been proved to be efficacious in the relief of motor symptoms in PD, while it can also lead to impulse control disorders such as pathological gambling due to its dopamine agonistic effects. PATIENT CONCERNS: A 28-year-old Chinese female patient with Parkinson disease and a history of taking piribedil finally developed pathological gambling and depressive episode. DIAGNOSES: After a careful clinical observation and evaluation, the patient met the criteria of severe depressive episode and pathological gambling due to antiparkinson therapy. INTERVENTIONS: We discontinued piribedil and picked bupropion, a dopamine reuptake inhibitor, to alleviate the depressive symptom. Benzhexol and selegiline were also added for the control of motor fluctuations. OUTCOMES: After 3 weeks' treatment, the patient's depressive mood was significantly alleviated and her recurring PD symptoms were also relieved. She was no more addicted to network gambling, and there was no recurrence during the 1-year follow-up. LESSONS: Piribedil-induced problem gambling and impulse control disorders are side effects needed to be evaluated when commencing a patient on piribedil. This case further emphasizes the importance of monitoring and controlling Parkinson symptoms after drug reduction or withdrawal. Anticipation of this risk strengthens the significance of detailed medical history-taking and targeted clinical management.

Anesthesia, sex and miscarriage history may influence the association between cesarean delivery and autism spectrum disorder.

BACKGROUND: To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association. METHODS: In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD. RESULTS: CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311-1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273-2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392-5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094-4.291; aOR = 2.919, 95% CI = 1.789-4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (ß = - 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD. CONCLUSIONS: The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.

Sleep Problems of Children with Autism May Independently Affect Parental Quality of Life.

The current study explored how and to what extent sleep problems in children with autism spectrum disorder (ASD) impacted their parents' quality of life (QOL). A total of 440 ASD children and 344 age-matched typically developing (TD) children were included in the case-control designed study. In the TD group, a linear regression model showed that the Children's Sleep Habits Questionnaire (CSHQ) total scores were negatively associated with maternal mental health summary (MCS) scores in the SF-36v2 (ß = - 2.831), while in the ASD group, the CSHQ total scores were negatively associated with the parental physical health summary (PCS) scores (ß = - 3.030 for mothers, ß = - 3.651 for fathers). Path analysis showed that sleep problems in ASD children had both direct and indirect effects on maternal PCS scores. The results indicated that sleep problems in children with ASD might affect parental QOL differently from TD children, and act as independent impact factors on parental physical health.

Glutathione S-transferase gene polymorphisms (GSTT1 and GSTM1) and risk of schizophrenia: A case-control study in Chinese Han population.

Schizophrenia (SCZ) is a chronic disability disorder related to oxidative stress. Glutathione S-transferase (GST) is a group enzyme that protects cells and tissues from oxidative stress damage. Among GSTs, GSTT1 and GSTM1 have well defined genetic polymorphisms. The purpose of our research was to explore the correlation between GSTT1 and GSTM1 polymorphism and SCZ risk in Chinese Han population.A total of 650 subjects (386 SCZ patients and 264 healthy individuals) were included in this case-control designed study. The GSTT1 and GSTM1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). We explored the relationship between these 2 polymorphisms and the risk of SCZ.We found that the GSTT1 null genotype had a protective effect on the development of SCZ [odds ratio (OR) = 0.601, 95% confidence interval (95% CI) = 0.412-0.986, P = .031]. We also found that the combination of null genotypes of the GSTT1 and GSTM1 genes was made at a lower risk of SCZ (OR = 0.452, 95% CI = 0.238-0.845, P = .028). However, we found no correction between Positive and Negative Syndrome Scale score (PANSS) and GSTM1, GSST1 genotypes in SCZ patients.Our finding revealed that GSTT1 null polymorphisms may be related to the reduced risk of SCZ in Chinese Han population, and this risk was further reduced with the combination of GSTT1 null polymorphisms and GSTM1 null polymorphisms.

Genotype and Phenotype Correlations for TBL1XR1 in Neurodevelopmental Disorders.

TBL1XR1 is a member of the WD40 repeat-containing gene family. Mutations of TBL1XR1 have been reported in neurodevelopmental disorders (NDDs). Although the phenotypes of some patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with TBL1XR1 mutations. Herein, we report a new de novo frameshift mutation in TBL1XR1 (NM_024665.4, c.388_389delAC, p.T130Sfs*14) in a patient with autism spectrum disorder (ASD). To explore the correlations between genotypes and phenotypes for TBL1XR1 in NDDs, we manually curated and analyzed 38 variants and the associated phenotypes from 50 individuals with NDDs. TBL1XR1 mutations lead to a wide range of phenotypic defects. We conclude that the most common phenotypes associated with TBL1XR1 mutations were language and motor developmental delay, intellectual disabilities, facial deformity, hypotonia, and microcephaly. Our study provides a comprehensive spectrum of neurodevelopmental phenotypes caused by TBL1XR1 mutations, which is important for genetic diagnosis and precision clinical management.

Peripheral non-enzymatic antioxidants in patients with schizophrenia: a case-control study.

BACKGROUND: Recent studies show that oxidative stress is associated with the pathogenesis of schizophrenia. There are two major types of antioxidant systems in vivo, namely enzymatic antioxidants and non-enzymatic antioxidants. This study investigated differences of non-enzymatic antioxidants between schizophrenia patients and healthy controls. METHODS: Peripheral UA, ALB, and TBIL of 107 schizophrenic patients in the acute stage and 101 in the remission stage were measured respectively, so were 273 healthy controls. RESULTS: The levels of UA (P = 0.020) and TBIL (P < 0.001) of schizophrenic patients in the acute stage were higher than those of healthy controls, while the level of ALB (P < 0.001) was lower. Similar results were detected form schizophrenic patients in the remission stage. Schizophrenic patients in the acute stage were divided into antipsychotics-use subgroup (n = 56) and antipsychotics-naïve/free subgroup (n = 51). The level of UA (P = 0.001) in the antipsychotics-use subgroup was higher than that in the antipsychotics-naïve/free subgroup, while the level of TBIL (P = 0.002) was lower than that in the antipsychotics-naïve/free subgroup. Seventy-seven schizophrenic patients in the acute stage were followed up, and there was no significant difference in the level of UA before and after treatment, but levels of ALB (P < 0.001) and TBIL (P < 0.001) decreased significantly after the treatment. CONCLUSION: This study demonstrated that the dysfunction of the peripheral non-enzymatic anti-oxidation system might be involved in the pathogenesis of schizophrenia.

Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.

The genotype-first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype-specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype-to-genotype approach, we performed whole-exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head-size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3) implicated in ASD and related neurodevelopmental disorders. We identify genotype-phenotype correlations for head-size-associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype-to-genotype strategy would accelerate the elucidation of genotype-phenotype relationships for ASD by using phenotype-restricted cohorts.

Correlation between GRIK2 rs6922753, rs2227283 polymorphism and aggressive behaviors with Bipolar Mania in the Chinese Han population.

OBJECTIVES: Animal studies have shown that glutamate receptor ionotropic kainate 2 (GRIK2) gene knockout mice are more impulsive and aggressive. This study aims to verify whether the rs6922753 and rs2227283 polymorphisms of the GRIK2 gene are associated with both aggressive behavior and bipolar mania in the Chinese Han population. METHODS: Polymerase chain reaction (PCR) was applied in the genotype rs6922753 and rs2227283 polymorphisms of the GRIK2 gene in 201 bipolar manic patients with aggressive behaviors, 198 bipolar manic patients without aggressive behaviors, and 132 healthy controls. The Modified Overt Aggression Scale (MOAS) was used to evaluate aggressive behavior in patients with bipolar mania. RESULTS: No correlation was found between aggressive behavior and the rs6922753 polymorphism in the three groups. The A/A genotype and A allele of the rs2227283 polymorphism were found significantly more frequently in patients with aggressive behavior than in healthy controls (p = .004 and p = .013, respectively) and in patients with nonaggressive behavior (p = .002 and p = .018, respectively). The A/A genotype and A allele were associated with an increased risk of aggressive behavior. CONCLUSION: This study suggests that the rs2227283 polymorphism of the GRIK2 gene is related to aggressive behaviors in bipolar manic patients and that the A/A genotype and A allele may increase the risk of the aggressive behavior in bipolar manic patients.

POGZ de novo missense variants in neuropsychiatric disorders.

BACKGROUND: De novo likely gene-disrupting variants of POGZ cause autism spectrum disorder (ASD) and intellectual disability. However, de novo missense variants of this gene were not well explored in neuropsychiatric disorders. METHODS: The single-molecule molecular inversion probes-based targeted sequencing method was performed on the proband. Variant was validated using Sanger sequencing in both proband and parents. Immunoblot analysis was performed to examine the expression of POGZ in patient-derived peripheral blood lymphocytes. Published POGZ de novo missense variants in neuropsychiatric disorders were reviewed. RESULTS: We detected a novel de novo missense variant in POGZ (c.1534C>A, p.H512N, NM_015100.4) in an individual with ASD. Immunoblot analysis revealed a dramatic reduction in POGZ protein in patient-derived peripheral blood lymphocytes suggesting a loss-of-function mechanism of this de novo missense variant. In addition, we collected and annotated additional eight POGZ de novo missense variants identified in neuropsychiatric disorders from literatures. CONCLUSION: Our findings will be beneficial to the functional analysis of POGZ in ASD pathogenesis, and for genetic counseling and clinical diagnosis of patients with POGZ de novo missense variants.

Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.

Background: We previously performed targeted sequencing of autism risk genes in probands from the Autism Clinical and Genetic Resources in China (ACGC) (phase I). Here, we expand this analysis to a larger cohort of patients (ACGC phase II) to better understand the prevalence, inheritance, and genotype-phenotype correlations of likely gene-disrupting (LGD) mutations for autism candidate genes originally identified in cohorts of European descent. Methods: We sequenced 187 autism candidate genes in an additional 784 probands and 85 genes in 599 probands using single-molecule molecular inversion probes. We tested the inheritance of potentially pathogenic mutations, performed a meta-analysis of phase I and phase II data and combined our results with existing exome sequence data to investigate the phenotypes of carrier parents and patients with multiple hits in different autism risk genes. Results: We validated recurrent, LGD, de novo mutations (DNMs) in 13 genes. We identified a potential novel risk gene (ZNF292), one novel gene with recurrent LGD DNMs (RALGAPB), as well as genes associated with macrocephaly (GIGYF2 and WDFY3). We identified the transmission of private LGD mutations in genes predominantly associated with DNMs and showed that parental carriers tended to share milder autism-related phenotypes. Patients that carried DNMs in two or more candidate genes show more severe phenotypes. Conclusions: We identify new risk genes and transmission of deleterious mutations in genes primarily associated with DNMs. The fact that parental carriers show milder phenotypes and patients with multiple hits are more severe supports a multifactorial model of risk.

Maternal dietary patterns, supplements intake and autism spectrum disorders: A preliminary case-control study.

The aim of this study was first to investigate associations between maternal dietary patterns and autism spectrum disorders (ASDs) and second to investigate association between maternal supplement intake and ASD.We used a case-control study design to enroll typically developing (TD) children and children with ASD, and data were derived from the Autism Clinical and Environmental Database (ACED).Three seventy four children with AUTISM and 354 age matched TD children were included. The multivariate logistic regression model revealed that maternal unbalanced dietary patterns before conception had a significant increased risk of ASD in offspring (mostly meat: adjusted OR, 4.010 [95% CI, 1.080, 14.887]; mostly vegetable: adjusted OR, 2.234 [95% CI, 1.009, 4.946]); maternal supplementation of calcium during pregnancy preparation was associated with decreased ASD risk (adjusted OR, 0.480 [95% CI, 0.276, 0.836]).This study provided preliminary evidence that maternal unbalanced dietary patterns may be a risk factor for ASD and supplementation of calcium during pregnancy preparation may be inversely associated with ASD in offspring.

Genotype and phenotype correlations for SHANK3 de novo mutations in neurodevelopmental disorders.

SHANK3 has been identified as the causative gene of 22q13.3 microdeletion syndrome phenotype. De novo mutations (DNMs) of SHANK3 were subsequently identified in patients with several neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia (SCZ), a Rett syndrome-like phenotype, and intellectual disability (ID). Although broad developmental phenotypes of these patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with SHANK3 DNMs. In this study, we identified a de novo splice mutation (NM_033517.1: c.2265+1G>A) that functionally impairs mRNA splicing, produces multiple splice variants, and results in the reduction of the amounts of mRNA. To analyze the genotype and phenotype correlations for SHANK3 DNMs, we reviewed 37 previously published patients with 28 SHANK3 DNMs. Our results revealed that haploinsufficiency of SHANK3 causes a broad spectrum of neurodevelopmental phenotypes with impaired social interaction, repetitive behavior, speech impairment, ID, and regression as the most common observations. Seizures, hypotonia, global development delay, dysmorphic features, and several other features also occurred recurrently. Specific phenotypes are also observed in certain genotypes. Our study provides the frequency of the heterogeneous co-occurring conditions caused by SHANK3 DNMs, which will be beneficial for diagnosis and clinical management.

Social impairment of children with autism spectrum disorder affects parental quality of life in different ways.

This study evaluated the life quality of Chinese parents of preschool children with autism spectrum disorder (ASD) and their association with child social impairment and childcare burden. The participants included 406 families of children with ASD and 513 families with typically developing (TD) children. The findings indicated that parents in the ASD group had a lower quality of life than parents in the TD group, whereas only mother of children with ASD experienced a greater childcare burden than mother with TD children. Lower parental quality of life were associated with higher social impairment of children. To further clarify the correlativity of child social impairment, parental quality of life and childcare burden, the mediation analyses were conducted. The results showed that childcare burden mediated the influence of child social impairment on maternal quality of life, while it has no mediating effect on fathers. It implies that social impairment of children affects parental quality of life in different ways.