Analysis of the characteristics of SPTB gene variants among 16 children with Hereditary spherocytosis / 中华医学遗传学杂志

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.

Standards for the interpretation of constitutional copy number gain: Recommendation from the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen) / 中华医学遗传学杂志

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.

The relationship between PLAGL1 methylation level and the risk of abnormal growth:a meta-analysis / 国际儿科学杂志

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.