Wei Gu

SOX11 variants have been associated with Coffin-Siris syndrome and a broader neurodevelopmental spectrum (IDDMOH), but their role in isolated or syndromic hypogonadotropic hypogonadism (HH) remains under-recognized. We report a 13-year-old Chinese girl who presented with delayed puberty (Tanner B1, PH1), infantile uterus and low basal gonadotropins. Trio whole-exome sequencing identified a de-novo heterozygous SOX11 c.346_348del (p.Tyr116del) variant. Olfactory and pituitary MRI revealed bilateral olfactory-bulb/nerve hypoplasia and a pituitary height of 3.4 mm, fulfilling Kallmann-syndrome criteria. GnRH-pump therapy restored gonadotropin output within 72 h. A systematic literature review of 32 additional SOX11-related HH cases (total n = 33) showed that 25/26 phenotyped individuals exhibited Coffin-Siris-compatible features, whereas 13/33 met Kallmann-syndrome criteria. Thirty unique variants were identified, 17/30 clustering within the HMG domain and 15/18 proven de-novo. SOX11 should be included in Kallmann syndrome gene panels. We propose "SOX11-related disorder" as an overarching diagnostic framework for all individuals with SOX11 likely pathogenic/pathogenic variants, mandating comprehensive baseline evaluation-including endocrine assessment, neurodevelopmental screening, and MRI of olfactory tracts and pituitary-regardless of initial presentation.

Culler-Jones syndrome (CJS)(OMIM: 615849) is a rare genetic disorder characterized by multiple anterior pituitary hormone deficiencies and variable polydactyly, caused by mutations in the GLI2 gene (OMIM: 165230). A 9-year- and 8-month-old male presented with multiple anterior pituitary hormone deficiencies and sensorineural deafness. Brain magnetic resonance imaging (MRI) demonstrated the pituitary stalk interruption syndrome (PSIS), characterized by anterior pituitary hypoplasia, absent pituitary stalk, and ectopic neurohypophysis.Whole-exome sequencing(WES) identified a heterozygous nonsense mutation (c.3640 C > T) in the GLI2 gene, likely resulting in premature protein truncation. In this study, we document a novel GLI2 gene mutation linked to Culler-Jones syndrome.

Background: Emerging evidence suggests the presence of distinct endotypes of Type 1 diabetes mellitus (T1DM): T1DE1 in individuals diagnosed at age < 7 years in contrast to T1DE2 in those diagnosed at ≥ 13 years of age. We aimed to comprehensively explore the phenotypic heterogeneity of T1DM with respect to the age‐related endotypes.Methods: This cross‐sectional study was conducted in China and involved 1204 children newly diagnosed with T1DM who were admitted to the pediatric department of a tertiary hospital from January 1, 2010 to December 31, 2023. The patients were divided into three age groups: < 7 years (T1DE1), 7–12 years, and ≥ 13 years (T1DE2). A comparison was made among the age groups regarding demographic characteristics, glucose metabolism, β‐cell autoimmunity, and metabolic decompensation.Results: Patients under 7 years exhibited a shorter symptom duration before diagnosis, along with the lowest fasting and postprandial C‐peptide and C‐peptide to glucose ratio levels and the highest postprandial glucose levels. They also showed the highest insulin autoantibody positivity rate and creatine kinase‐MB levels. In contrast, patients aged 13 and older had the highest HbA1c levels and glutamate decarboxylase antibody positivity rate. In addition, this group showed the highest prevalence of TPOAb and TgAb positivity, as well as the largest proportion of abnormal liver function cases.Conclusions: The study illustrates age‐specific phenotypic heterogeneity in pediatric T1DM, indicating the presence of distinct endotypes. Further investigation of these endotypes may offer more evidence for the precise treatment of T1DM.

This study aims to characterize and analyze the expression of representative biomarkers like lymphocytes and immune subsets in children with thyroid disorders. It also intends to develop and evaluate a machine learning model to predict if patients have thyroid disorders based on their clinical characteristics, ultimately providing insights to enhance the clinical guidelines for the pathogenesis of childhood thyroid disorders. This cross-sectional study conducted in China examined diagnosed cases to describe the characteristics and expression of lymphocyte and immune subsets as predicted by the model. The study included two groups of children: 139 who were hospitalized in the Department of Endocrinology and a control group consisting of 283 children who underwent routine health checks at the Department of Children Healthcare. Cases were classified into three groups based on diagnoses: Graves’ disease (GD), Hashimoto’s thyroiditis (HT), and hypothyroidism. By employing 11 readily obtainable serum biochemical indicators within three days of admission, the median concentrations and percentages of subset measurements were analyzed. Additionally, nine machine learning (ML) algorithms were utilized to construct prediction models. Various evaluation metrics, including the area under the receiver operating characteristic curve (AUC), were employed to compare predictive performance. GD cases had increased levels of CD3-CD19 + and CD3 + CD4 + T lymphocytes, and a higher CD4+/CD8 + ratio. In both GD and HT, the levels of complement C3c, IgA, and IgG were higher than those in the control group. HT cases also had an increasing percentage of CD3-CD16 + 56 + T lymphocytes. Most immune markers increased in hypothyroidism, except for some T lymphocyte percentages and the CD4+/CD8 + ratio. To reduce age-related bias, propensity score matching was used, yielding consistent results. Among the nine machine learning models evaluated, logistic regression showed the best performance, being useful in clinical practice. Specific lymphocytes with different biomarkers are positively correlated with autoimmune thyroid disease (AITD) in children. Complement proteins C3c and C4, along with IgG, IgA, IgM, and T/B cells, are significant in childhood thyroid diseases. Our best model can effectively distinguish these conditions, but to enhance accuracy, more detailed information such as clinical images might be needed.

There is a delay in the clinical diagnosis of Turner syndrome (TS), particularly for patients with mosaic karyotypes. This diagnostic delay can hinder age-appropriate treatments and lead to adverse health outcomes. Therefore, it is necessary to explore improvement measures for early diagnosis and treatment plans based on the current clinical situation. Furthermore, as research progresses, the focus of clinical diagnosis and treatment of TS is gradually expanding to multiple aspects, including cardiovascular health, fertility, and transitional care, in order to improve the prognosis and quality of life of the patients. This paper discusses the current clinical status and management key points of TS diagnosis and treatment, aiming to provide insights for improving the management of TS.

Background Single gene variants that give rise to neonatal diabetes mellitus (NDM), maturity onset diabetes of the young (MODY) and syndromic forms of diabetes mellitus (SDM) are responsible for 3.1-4.2% of all diabetes cases. This single-center study with a relatively larger sample size aimed to evaluate the clinical and genetic characteristics of Chinese children with suspected monogenic diabetes (MD) using next generation sequencing (NGS) methods. Materials and Methods Data were collected from 1550 consecutive children diagnosed with diabetes/hyperglycemia at the Endocrinology Department of Children’s Hospital of Nanjing Medical University from 2012 to 2023. The genotype and phenotype of 138 children with suspected MD were retrospectively analyzed. Results Among 138 children, 16, 97, and 25 patients with NDM, suspected MODY and SDM were assessed by NGS, with a pick-up rate of 87.5%, 57.8%, and 56%, respectively. In total, there was a high pick-up rate of MD, with 58% (80 of 138) among antibody-negative pediatric patients. Pathogenic variants were found in GCK, HNF1A, INS, KCNJ11, INSR, HNF4A, ABCC8, WFS1, ALMS1, HNF1B, BLK and ZFP57 genes with 13 novel variants in addition to 4 patients with CNVs. In this cohort, GCK-MODY was the leading cause and the mildest type of MODY. GCK-MODY displayed favorable lipid profile when compared to non-GCK-MODY and MODYX, which might be cardioprotective. Following an accurate genetic diagnosis of diabetes, 19 patients switched from insulin therapy to oral agents or lifestyle interventions. Conclusion NGS tests helped to identify the precise etiology of monogenic diabetic patients which has implications for better individualized management.

Over the decades the trends of early onset of puberty have been observed in children, particularly in girls. Research evidence has reported diet to be among the most important risk factors for puberty onset. This study evaluated the association between dietary behavior and puberty in girls. We enrolled 201 girls with the main complaints of breast development as the cases at the Endocrine Department of Nanjing Children's Hospital. The cases were divided into breast development with central priming and breast development without central priming groups and were matched with 223 normal health girls with no breast development (control group). We used the modified Child Eating Behavior Questionnaire (CEBQ) to conduct a face-to-face interview about dietary behavior. Sample t-test or Mann Whitney U test or Chi-square test, the analysis of variance or Kruskal Wallis test, and least significant difference (LSD) were used to compare differences between the groups, Bonferroni was used to correct the p-value, and logistic regression was used to analyze risk factors for puberty onset. A total of 424 girls participated in this study, among them, 136 were cases with breast development with central priming, 65 were cases with breast development without central priming, and 223 were normal health girls with no breast development. Age of the participants ranged from 4.5 to 9.3 years. There were significant differences in food response (p < 0.001), dietary restriction (p < 0.001), frequencies of vegetable intake (χ2 = 8.856, p = 0.012), drinking milk (χ2 = 23.099, p = 0.001), and borderline statistical difference in a total score of unhealthy dietary behavior (p = 0.053) among the cases and controls. However, in the post hoc analysis, these dietary behaviors were significant differences between the girls with breast development with central priming and the control groups. Moreover, girls in the breast development with central priming group had significantly higher bone age (BA), uterine body length, ovarian volume, basal luteinizing hormone (LH), basal follicle-stimulating hormone (FSH), peak LH, peak FSH, estradiol (E2), and free triiodothyronine (FT3) compared to those in the breast development without central priming group. In the multivariate logistic regression, only uterine body length was associated with increased risk of breast development with central priming (OR = 1.516, 95%CI: 1.243–1.850). There were significant differences in dietary behaviors among girls with breast development with central priming and normal health girls with no breast development, and uterine body length was associated with an increasing risk of breast development with central priming among girls with breast development.

There is an argument that BPA substitutes may have the same or more deleterious health effects as BPA due to their structural similarity. This study explored the association between urinary BPA substitutes and precocious puberty among girls by including 120 girls with precocious puberty (cases) aged 2–10 years enrolled at Nanjing Children’s Hospital Department of Endocrinology in China between April 2021 to September 2021 and 145 healthy girls (controls) recruited from a primary school. Logistic regression was used to evaluate the effect of single exposures, and Bayesian kernel machine regression (BKMR) and quantile-based g-computation were used for the mixed effect. In the multivariate logistic regression, BPS (bisphenol S), TBBPA (tetrabromobisphenol A), and BPFL (bisphenol-FL) were significantly associated with increased risk of precocious puberty (odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.13, 2.76, p = 0.014), (OR = 1.46, CI: 1.06, 2.05; p = 0.023), and (OR = 1.47, CI: 1.01, 2.18; p = 0.047), respectively. The BMKR and quantile-based g-computation models revealed consistent associations for single exposures and there was insufficient evidence for the associations of the mixed exposure of bisphenols with precocious puberty. In conclusion, BPA substitutes such as BPS, TBBPA, and BPFL may be associated with an increased risk of precocious puberty in girls.

Background: Since the COVID-19 pandemic outbreak, diabetes mellitus (DM) has been at the core of the confirmed risk factors for fatal or critical care unit-treated COVID-19 and COVID-19 related complications. Although relevant studies on DM have developed rapidly during the COVID-19 pandemic. However, the aforementioned research results have not been systematically quantified by means of bibliometric analysis.Purpose: The purpose of this study is to provide a comprehensive analysis of the current status and trends of publications related to DM research during the COVID19 epidemic.Methods: A bibliometric analysis was performed using the Web of Science database. In this study, we used citespace, R software and R-Bibliometrix to analyze keywords, most-cited authors, most-cited countries, most-cited global documents, and co-occurrence and co-citation networks.Results: A total of 1688 publications was included in this study. Investigators from the United States contributed the most publications. The United States, China and Europe have the most collaboration with the other countries/regions. A total of 3355 institutions made contributions to this study. Of the top 10 institutions with the most publications, N8 Research Partnership showed the most centrality. Among the top 10 journals, Diabetes Research and Clinical Practice published the most articles. Among authors included, Khunti Kamlesh is rated first with 27 papers and has the highest centrality. The most frequently co-cited article is entitled “Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study”. The most popular keywords included diabetes, mortality, diabetes, outcome, occurrences, risk, and type 1 diabetes.Conclusion: This bibliometric study provides an overall picture of DM research and research trends during the COVID-19 pandemic and provides a basis for researchers to develop their next research strategies.