In this paper , based on the analysis of the facing predicament of current situation of medical ethics education , the authors combined with the practice of medical ethics education and the school experience , based on the theory of life education , put forward to experience the activities of public medical treatment building practice of medical students medical ethics education system , promote the educational work to carry out the practice of medical colleges, improve the teaching quality of medical ethics education .

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Child ; DNA Copy Number Variations ; Female ; Genetic Testing ; Genetics, Medical ; Genome, Human/genetics* ; Genomics ; Humans ; Pregnancy ; United States

OBJECTIVE: To analyze the clinical characteristics and spectrum of SPTB gene variants among 16 Chinese children with Hereditary spherocytosis (HS) and explore their genotype-phenotype correlation. METHODS: Sixteen children who were diagnosed with HS at the Affiliated Hospital of Capital Institute of Pediatrics from November 2018 to July 2022 were selected as the research subjects. Genetic testing was carried out by whole exome sequencing. Candidate variants were verified by Sanger sequencing and subjected to bioinformatic analysis and prediction of 3D structure of the protein. Correlation between the SPTB genotypes and clinical phenotypes was analyzed using Chi-squared test. RESULTS: The male-to-female ratio of the HS patients was 6 : 10, with the median age being 7-year-and-10-month. Clinical features of the patients have included anemia, reticulocytosis and gradual onset of splenomegaly. Mild, moderate and severe anemia have respectively occurred in 56.25% (9/16), 31.25% (5/16) and 12.50% (2/16) of the patients. SPTB gene variants were detected in all patients, among which 10 were unreported previously and 7 were de novo in origin. Loss of function (LOF) variants accounted for 93.75% (15/16). Only one missense variant was detected. Eleven, 4 and 1 of the variants had occurred in the repeat domain, CH1 domain, and dimerization domain, respectively. There was no significant correlation between the type or domain of the SPTB gene variants with the clinical features such as severity of anemia (x² = 3.345, P > 0.05). All of the variants were predicted to be pathogenic or likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION Mild to moderate anemia are predominant clinical features of the HS children harboring a SPTB gene variant, for which LOF variants are the main mutational type. The clinical feature of HS is unaffected by the type of the variants.
Child ; Female ; Humans ; Male ; Computational Biology ; Genetic Testing ; Genomics ; Genotype ; Spherocytosis, Hereditary/genetics* ; East Asian People/genetics* ; Spectrin/genetics*

Objective:To investigate the phenotypes of Rubinstein-Taybi syndrome (RSTS) caused by variants in the CREBBP or EP300 gene, and the correlation between genotype and phenotype.Methods:This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022. Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing, chromosomal microarray analysis, or copy number variation sequencing (CNV-seq). The variant categories were summarized and phenotype numbers were re-visited for RSTS patients. Based on variant types, the patients were divided into different groups (point variant or copy number deletion, EP300 or CREBBP point variant, and loss of function or missense variant). Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results:A total of 21 RSTS patients were recruited, including 12 males and 9 females, with ages ranging from 1 month to 14 years and 2 months. Among them, 67% (14/21) had point variants, and 33% (7/21) had copy number deletions. Out of these, 20 variants (95%) were de novo. Among 20 patients finishing phenotype count during re-visit, 95% (19/20) of the patients exhibited developmental delays before the age of 2 years. Additionally, 80% (16/20) of the patients had distinctive facial features. Considering phenotype count, no statistically significant difference was found between point variant (14 cases) and copy number deletion (6 cases) (5.0 (3.0, 7.0) vs. 5.0 (2.5, 5.3), Z=0.75, P=0.452), CREBBP (10 cases) and EP300 gene (4 cases) point variant (5.0 (3.8, 7.0) vs. 4.0 (2.0, 6.0), Z=1.14, P=0.253), and loss of function (9 cases) and missense (5 cases) variant (6.0 (4.5, 7.0) vs. 3.0 (2.5, 5.5), Z=1.54, P=0.121). Conclusions:Patients with RSTS primarily exhibit developmental delays in early childhood. Specific facial features serve as suggested signs of genetic testing. However, no significant genotype-phenotype correlation is found.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.

Objective Studies and researches have indicated that the methylation level of PLAGL1 differentially methylated region (DMR) was associated with some development disorder syndromes.This project is purposed to prove whether methylation levels of PLAGL1 DMR is related to the fetal and early postnatal development.Methods We performed a meta-analysis of the published data on PLAGL1 DMR methylation levels in children with developmental disorders compared with that in normal children.Results PubMed,Medline,EMBASE,WanFang databases were systematically searched to identify relevant studies.We included 7 studies in this meta-analysis,with a total of 195 cases and 438 controls concerning 6 kinds of developmental disorder syndromes.The methylation level of PLAGL1 DMR was lower in children with abnormal growth (excess growth or retarded growth) than that in normal children,with a pooled percentage mean methylation difference (95％ confidence intervals) of-1.05 (-1.93,-0.17).On this basis,we analyzed the odds ratio (95％ confidence intervals) of hypomethylation of PLAGL1 DMR in abnormal growth children in comparison with normal children.The combined odds ratio (95％ confidence intervals) of hypomethylation in abnormal growth children is 2.18 (1.23,3.88) in comparison with normal children.Conclusion Hypomethylation of PLALG1 is actually a risk factor of suffering abnormal growth for children.