Whole exome sequencing analysis of a patient with 45,X/46,XY mosaicism and autism spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD).@*METHODS@#Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter.@*RESULTS@#The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance.@*CONCLUSION@#Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.

A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio / 中华医学遗传学杂志

OBJECTIVE@#To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene.@*METHODS@#The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant.@*RESULTS@#The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function.@*CONCLUSION@#The KIF1A gene may be a risk gene for ASD.

Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders / 中华医学遗传学杂志

Objective@#To explore susceptibility genes for autism spectrum disorders (ASD).@*Methods@#Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates.@*Results@#A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2 (0.8146)] and four medium-confidence genes [ERBB2 (0.1322), LAMC3 (0.1117), PPFIA4 (0.1059), DISC1 (0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes.@*Conclusion@#Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders / 中华医学遗传学杂志

OBJECTIVE@#To explore susceptibility genes for autism spectrum disorders (ASD).@*METHODS@#Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates.@*RESULTS@#A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2(0.8146)] and four medium-confidence genes [ERBB2(0.1322), LAMC3(0.1117), PPFIA4(0.1059), DISC1(0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes.@*CONCLUSION@#Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Behavioral phenotypes of autism spectrum disorder patients and their parents / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the behavior phenotypes of patients with autism spectrum disorder (ASD) and their parents through family study.</p><p><b>METHODS</b>Forty-five core families with ASD and 30 control families from Chengdu area were examined using Autism Spectrum Quotient (AQ). Descriptive statistical analysis, correlation analysis, and Logistic regression analysis were used to investigate the effect of various factors, especially genetic factors that may affect the pathogenesis of ASD.</p><p><b>RESULTS</b>The social skills factor and communication factor of the father's AQ scale, as well as the mother's age of childbearing and AQ social skills factor are related to whether children with ASD (R were 0.46, 0.39, 0.39 and 0.36, P<0.05). The communication factor of the parents' AQ and mother's attention to detail factor are related to whether children will show developmental anomaly before the age of 36 months (R were 0.55, 0.51 and 0.54, P<0.05). The social skill problems of parents and father's communication problems are risk factors for children with autism.</p><p><b>CONCLUSION</b>ASD may be influenced by both genetic and environmental factors. The autistic behavior phenotype of parents is a risk factor for ASD and is associated with developmental anomalies of early childhood.</p>

The prevalence and risk factors for non-suicidal self injury among middle school students / 中华行为医学与脑科学杂志

Objective To investigate the prevalence and risk factors of non?suicidal self injury among middle school students. Methods Data were collected from 2 140 middle school students with the mean age of 13.92 by stratified sampling method. All students were evaluated with Beck Depression Scale (BDI),Barratt Im?pulsiveness Scale ( BIS ) , Adolescent Self?Rating Life Events Check List ( ASLEC ) , Adolescents Health related Risk Behaviors Inventory ( AHRBI ) , Chinese version of Family Adaptability and Cohesion Evaluation Scales ( FACES II?CV) ,and self?made investigate questionnaire. Results The prevalence of non?suicidal self injury a?mong local middle school students was 23.2%,total 495 adolescents were endorsed non?suicidal self injury,and 49.7% were girls.The results of in multivariable logistic regression showed the main risk factors for non?suicidal self injury among adolescents were being female,depressive symptoms,impulsiveness,negative life events and health re?lated risk behaviors. Conclusion Non?suicidal self injury is high among Chinese adolescent in the city of Dujian?gyan,and it is necessary to take effective interventions.

The critical point research of the children's revised impact of event scale of Chinese edition / 中华行为医学与脑科学杂志

Objective The Children's Revised Impact of Event Scale (CRIES-13) is used for Screening PTSD of children. The reliability and validity of CRIES-13 is good. To research the demarcation points of CRIES-13 (Chinese version) based on the reliability and validity analysis,and to improve the useful value of the scale.Methods In late September 2008, according affected condition, students were choosed who were fit for the research standard as subjects in two middle schools. First,general questionnaire (self-writing) and CRIES-13 were applied to the subjects. Second, according to K-SADS-PL, physician carried out diagnosis meeting and evaluation to 310 students who were classified by stratified rand sampling. Critical point of CRIES-13 was divided by K-SADSPL. The assessment value of it were sensitivity, specificity, veracity, PPV, NPV. The right choice of division was measured by ROC curve. Results When the critical score was higher than 30, the score of Se ( 0. 833 ), Sp(0. 836) and NPV (0.97) was in the high level. Conclusion When the critical score is higher than 30, the scale have a good discrimination for PTSD, non-PTSD and it can be used extensively.

The reliability and validity research of the children's revised impact of event scale of Chinese edition / 中华行为医学与脑科学杂志

Objective To test the reliability and validity of CRIES-13(Chinese edition). The Children Revised Impact of Event Scale (CRIES-13) was recommened for diagnosing PTSD of children. Methods In the last third of the September 2008,according to the suffering condition,600 students were choosed who were fit for the research standard as subjects in two middle schools randomly. The viability of CRIES-13 was weighted by testretest reliability,Cronbach' s alpha,Split half reliability. The validity of CRIES-13 was analysed by content validity ,criterion validity,construction validity. Results In the test-retest reliability of CRIES-13, the Spearman correlation coefficient of total,intrusion factor,avoid factor,high warkening factor were 0.79, 0.75, 0.71, 0.75. Significant correlation were found among these scores. The Cronbach' s alpha of population was 0. 81. The Cronbach' s alpha of three factors was 0. 79 ( intrusion factor) , 0. 71 ( avoid factor), 0. 65 ( high awarkening factor). CRIES-13's split-half reliability was 0. 85. In the content validity test,the Spearman rank correlation coefficient between total score and each item was 0. 83 (intrusion factor), 0. 75 (avoid factor), 0. 85 (high awarkening factor). The correlation between intrusion factor and avoid factor was 0.63. The correlation between avoid factor and high awarkening factor was 0.41. The correlation between intrusion factor and high awarkening factor was 0.41. In struction validity, variance orthogonal rotation factor analysis was adopted and got three general factors. Their cumulative contribution to total variance was 55.52%. In the criterion validity test,significant correlation was found between intrusion factor and SDQ emotional factor and depression scale total score. Significant correlation was found between high awakening factor and SDQ emotional factor and depression scale total score. Conclusion The reliability and validity of CRIES-13 was good. It could be used extensively.

The effect of genetic and environmental factors on the internalizing behavior of children: a twin study / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the impacts of genetic and environmental factors on the internalizing behaviors of children using quantitative genetic analysis designed for twin study.</p><p><b>METHODS</b>One hundred and eighty nine twin pairs aged 6-16 years were studied using parental information of Achenbach Child Behavior Checklist, Family Adaptability and Cohesion Evaluation Scales-II and General Health Questionnaire-12. The heritability of the internalizing behavior of children was also estimated.</p><p><b>RESULTS</b>(1) The heritability of the internalizing behavior of the children was 0.54, which differed in different age and sex. (2) Family adaptability and parental mental health status had significant correlation with the internalizing behavior of children (r=-0.213, 0.250, 0.309, respectively, Ps <0.001),especially the mental health status of the mother (OR=2.483, P=0.008).</p><p><b>CONCLUSION</b>The internalizing behavior of children was influenced by genetic and environmental factors including family function and parental mental health status. It differed in different age and sex.</p>

A Prospective Twin Registry in Southwestern China: exploring the effects of genetic and environmental factors on cognitive and behavioral development and mental health well-being in children and adolescents / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>The goals, prospects and methods of the Prospective Twin Registry in Southwestern China (TRiSC) are described. The aim of this study is to measure children's behavioral development and psychopathology from phenotypic, genetic and environmental perspectives.</p><p><b>METHODS</b>The children's self-report, as well as parental and teachers' informant report were used to measure the children's behavior and psychopathology, and the latter was related to the children's general cognitive abilities, and to the parenting style. Other variables of interest such as children's temperament and parental health status were also used.</p><p><b>RESULTS</b>Nine thousand and three hundred thirty nine pairs of 0-16 years old twins have been registered, 324 pairs of them were monozygotic based on DNA samples as well as the detailed information on behavioral and cognitive aspects.Analysis has been performed for the influences of genetic and environmental factors on children's behavior and cognition.</p><p><b>CONCLUSION</b>School-based twins recruitment is a helpful method in child and adolescent twin study. TRiSC has been a valuable resource for research on the development of children's behavior and cognition.</p>