OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Objective To explore the correlation between plasma T cell subsets,serum interleukin-6(IL-6)levels and CT imaging characteristics in children with mycoplasma pneumoniae pneumonia(MPP),as well as its predictive value for clinical prognosis.Methods A total of 98 children with MPP were selected as the research subjects and divided into the good prognosis group(n=62)and the poor prognosis group(n=36)according to the clinical prognosis.The correlations between plasma T cell subsets,IL-6 levels,CT imaging characteristics and prognosis were analyzed.The predictive efficacy of plasma T cell subsets and IL-6 levels for poor progno-sis was analyzed.Results The levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),IL-6,CD8+and CD19+in the poor prognosis group were significantly higher than those in the good prognosis group,while the levels of CD3+,CD4+,CD4+/CD8+and CD16+/CD56+were significantly lower than those in the good prognosis group(P＜0.05).The statistical conditions of CT ima-ging characteristics such as pulmonary consolidation,ground-glass change,involvement of lung lobes ≥ 2,patchy consolidation shad-ows,grid nodular shadows,bronchial wall thickening,hilar lymph node enlargement,pleural effusion,and atelectasis in the poor prognosis group were significantly higher than those in the good prognosis group(P＜0.05).CD3+,CD4+,CD8+,CD4+/CD8+,CD19+,CD16+/CD56+and IL-6 had independent correlations with the above CT imaging characteristics.IL-6,CD8+and CD19+were positively correlated with the risk of poor prognosis,while CD3+,CD4+,CD4+/CD8+and CD16+/CD56+were negatively correlated with the risk of poor prognosis(P＜0.05).Individual detection of CD3+,CD4+,CD8+,CD4+/CD8+,CD19+,CD16+/CD56+,IL-6 and the combined detection of the seven indicators had certain predictive value for the occurrence of poor prognosis in patients[area under the curve(AUC)＞0.7].Conclusion Plasma T cell subsets and serum IL-6 levels are important factors influencing the prognosis of children with MPP and are independently related to the CT imaging characteristics.

Objective To investigate the expression levels of serum hemoglobin β(HBB)in hepatocellular carcinoma(HCC)patients and its correlation with topoisomeraseⅡα(TOP2A)gene.Methods A total of 48 HCC patients visited the Second Affiliated Hospital of Nantong University from August 2023 to September 2024 were selected as the HCC group,and 32 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.Their blood samples were collected,and the ex-pression levels of serum HBB and TOP2A genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Then,the relationship between the expression of HBB gene and clinicopathological parameters of the patients was ana-lyzed.The Kaplan-Meier Plotter database was used to evaluate the relationship between the expression of HBB gene and the prognosis of HCC.The diagnostic value of the expressions of serum HBB and TOP2A genes for HCC was assessed by the receiver operating charac-teristic(ROC)curve.Spearman rank correlation analysis was used to evaluate the correlation between the expressions of serum HBB and TOP2A genes in HCC patients.The regulatory effect of HBB gene on TOP2A gene was verified by the cell experiment.Results The expression levels of serum HBB gene in HCC patients(0.097[0.055,0.155])were significantly lower than that in healthy controls(1.029[0.625,1.434],U=19,P＜0.001).The expression levels of serum TOP2A gene in HCC patients(1.810[0.825,3.623])were significantly higher than that in healthy controls(1.047[0.604,1.364],U=495,P=0.007).The expression level of serum HBB gene in HCC patients was significantly negatively correlated with that of TOP2A gene(ρ=-0.384,P=0.007).The analysis results of clinicopathological parameters showed that the expression level of HBB gene was only related to tumor size(χ2=4.090,P＜0.05).The Kaplan-Meier survival analysis showed that the 5-year overall survival rate of the patients with low expression of HBB gene was signifi-cantly lower than that with high expression(HR=0.680,95%CI:0.470-0.970,P＜0.05).The analysis of the ROC curve showed that the area under the ROC curve(AUCROC)of HBB gene in diagnosing HCC was 0.987(95%CI:0.963-1.000).When the cut-off value was 0.228,its sensitivity was 100%and specificity was 97%.The AUCROC of TOP2A gene for the diagnosis of HCC was 0.677(95%CI:0.559-0.797).When the cut-off value was 1.285,its sensitivity was 65%and specificity was 75%.The combined detection of HBB and TOP2A genes for the diagnosis of HCC had an AUCROC of 0.988(95%CI:0.965-1.000).When the cut-off value was 0.657,its sensitivity was 100%and specificity was 97%.The cell experiment results showed that the overexpression of HBB gene could inhibit the expression of TOP2A gene,while the knockout of HBB gene had the opposite effect.Conclusion HBB gene is lowly expressed in the serum of HCC patients and is significantly negatively correlated with the expression of TOP2A gene.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

Objective:To analyze the clinical characteristics of familial hypercholesterolemia (FH) in children and provide a basis for clinical diagnosis and individualized treatment.Methods:Case series study. Clinical data of 24 children with FH, who were admitted to the Department of Endocrinology in Capital Center for Children′s Health, Capital Medical University, from January 2018 to January 2025, were analyzed. Follow-ups were performed every 3-6 months and ended in January 2025. According to the results of genetic testing, the children were divided into homozygous familial hypercholesterolemia (HoFH) group and heterozygous familial hypercholesterolemia (HeFH) group. The blood lipid levels of different subtypes, the efficacy of different treatments, and clinical outcomes were compared by Mann-Whitney U test. Results:The 24 children were from 17 families, including 14 males and 10 females, with a diagnostic age of 5.0 (3.0, 9.5) years. Genetic testing results showed that 22 cases (92%) had LDLR gene variants and 2 cases (8%) had APOB gene variants, all of which were inherited from parents. There were 5 cases (21%) of HoFH and 19 cases (79%) of HeFH, and 4 previously unreported new loci were identified. There were 6 children (25%) presented with xanthomas, including 5 cases of HoFH and 1 case of HeFH. The level of low-density lipoprotein cholesterol (LDL-C) in the HoFH group was significantly higher than that in the HeFH group ( P<0.05). Regarding treatment, 11 children received dietary control without taking medicine, 6 were treated with statins, 3 with ezetimibe, and 3 with statins combined with ezetimibe, and 1 underwent liver transplantation. None of the children receiving only dietary control achieved the target LDL-C level (<3.49 mmol/L or a reduction of >50%), and there was no statistically significant difference in LDL-C before and after dietary control ( P=0.158). After treatment with statins and (or) ezetimibe, LDL-C decreased in 12 children ( P<0.05); among them, 6 cases (all HeFH) reached the target LDL-C level. There was no statistically difference in LDL-C levels before and after treatment with atorvastatin and ezetimibe in 5 HoFH children( P>0.05). One HoFH child had LDL-C reduced to the normal range after liver transplantation. No serious adverse reactions were observed in all children during drug treatment. In the detection of vascular-related complications among 12 HeFH children, only 1 child had a slight thickening of the bilateral carotid intima-media, while no abnormalities were found in the others. Conclusions:Xanthoma is a characteristic manifestation of FH, but its incidence is relatively low in HeFH children. Family history and genetic testing are key evidences for the diagnosis of FH. Dietary control has limited efficacy in children with FH, and drug treatment should be initiated as early as possible. LDL-C levels in HoFH children are more difficult to control, if drug treatment shows poor efficacy, liver transplantation may be a better option.

Objective Summarize the endocrine characteristics of 5 children with Wiedemann-Steiner syndrome(WDSTS)to enhance the early recognition capability of clinicians for this condition.Methods A retrospective analysis of the medical history,clinical manifestations,genetic testing,and treatment of 5 children with Wiedemann-Steiner syndrome treated in the endocrinology department of capital center for children's health,capital medical university from October 2020 to December 2024,summarizing the clinical characteristics of the disease.Results Among the 5 cases of WDSTS,there were 2 males and 3 females,with ages ranging from 1.9 to 10 years at the time of diagnosis.Cases 1 and 3 were born prematurely,and cases 1,2 and 5 were diagnosed as small for gestational age(SGA)infants.All 5 children exhibited distinctive facial features,hirsutism,sacral dimple,developmental delay,and adenoid hypertrophy,premature tooth replacement,feeding difficulties,and a high incidence of urinary system abnormalities.Four children complained of slow growth.Cases 1 and 4 were diagnosed with short stature.Cases 3 and 5 had normal height but were slightly shorter with advanced bone age.Case 5 also experienced early puberty.Case 2 was diagnosed with premature adrenarche and idiopathic central precocious puberty due to the presence of pubic hair and breast enlargement.Cases 1 and 3 were treated with recombinant human growth hormone(rhGH),which resulted in significant height growth(approximately 10 cm/year).However,treatment was discontinued in Case 1 due to a significant advancement in bone age.Conclusions WDSTS should be considered in patients presenting with short stature,distinctive facial features,hirsutism,developmental delay,and multiple system deformities.While rhGH treatment can help improve height in these patients,the potential for accelerated bone age maturation during treatment requires careful monitoring.

Objective To investigate the expression levels of serum hemoglobin β(HBB)in hepatocellular carcinoma(HCC)patients and its correlation with topoisomeraseⅡα(TOP2A)gene.Methods A total of 48 HCC patients visited the Second Affiliated Hospital of Nantong University from August 2023 to September 2024 were selected as the HCC group,and 32 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.Their blood samples were collected,and the ex-pression levels of serum HBB and TOP2A genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Then,the relationship between the expression of HBB gene and clinicopathological parameters of the patients was ana-lyzed.The Kaplan-Meier Plotter database was used to evaluate the relationship between the expression of HBB gene and the prognosis of HCC.The diagnostic value of the expressions of serum HBB and TOP2A genes for HCC was assessed by the receiver operating charac-teristic(ROC)curve.Spearman rank correlation analysis was used to evaluate the correlation between the expressions of serum HBB and TOP2A genes in HCC patients.The regulatory effect of HBB gene on TOP2A gene was verified by the cell experiment.Results The expression levels of serum HBB gene in HCC patients(0.097[0.055,0.155])were significantly lower than that in healthy controls(1.029[0.625,1.434],U=19,P＜0.001).The expression levels of serum TOP2A gene in HCC patients(1.810[0.825,3.623])were significantly higher than that in healthy controls(1.047[0.604,1.364],U=495,P=0.007).The expression level of serum HBB gene in HCC patients was significantly negatively correlated with that of TOP2A gene(ρ=-0.384,P=0.007).The analysis results of clinicopathological parameters showed that the expression level of HBB gene was only related to tumor size(χ2=4.090,P＜0.05).The Kaplan-Meier survival analysis showed that the 5-year overall survival rate of the patients with low expression of HBB gene was signifi-cantly lower than that with high expression(HR=0.680,95%CI:0.470-0.970,P＜0.05).The analysis of the ROC curve showed that the area under the ROC curve(AUCROC)of HBB gene in diagnosing HCC was 0.987(95%CI:0.963-1.000).When the cut-off value was 0.228,its sensitivity was 100%and specificity was 97%.The AUCROC of TOP2A gene for the diagnosis of HCC was 0.677(95%CI:0.559-0.797).When the cut-off value was 1.285,its sensitivity was 65%and specificity was 75%.The combined detection of HBB and TOP2A genes for the diagnosis of HCC had an AUCROC of 0.988(95%CI:0.965-1.000).When the cut-off value was 0.657,its sensitivity was 100%and specificity was 97%.The cell experiment results showed that the overexpression of HBB gene could inhibit the expression of TOP2A gene,while the knockout of HBB gene had the opposite effect.Conclusion HBB gene is lowly expressed in the serum of HCC patients and is significantly negatively correlated with the expression of TOP2A gene.

Objective To explore the correlation between plasma T cell subsets,serum interleukin-6(IL-6)levels and CT imaging characteristics in children with mycoplasma pneumoniae pneumonia(MPP),as well as its predictive value for clinical prognosis.Methods A total of 98 children with MPP were selected as the research subjects and divided into the good prognosis group(n=62)and the poor prognosis group(n=36)according to the clinical prognosis.The correlations between plasma T cell subsets,IL-6 levels,CT imaging characteristics and prognosis were analyzed.The predictive efficacy of plasma T cell subsets and IL-6 levels for poor progno-sis was analyzed.Results The levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),IL-6,CD8+and CD19+in the poor prognosis group were significantly higher than those in the good prognosis group,while the levels of CD3+,CD4+,CD4+/CD8+and CD16+/CD56+were significantly lower than those in the good prognosis group(P＜0.05).The statistical conditions of CT ima-ging characteristics such as pulmonary consolidation,ground-glass change,involvement of lung lobes ≥ 2,patchy consolidation shad-ows,grid nodular shadows,bronchial wall thickening,hilar lymph node enlargement,pleural effusion,and atelectasis in the poor prognosis group were significantly higher than those in the good prognosis group(P＜0.05).CD3+,CD4+,CD8+,CD4+/CD8+,CD19+,CD16+/CD56+and IL-6 had independent correlations with the above CT imaging characteristics.IL-6,CD8+and CD19+were positively correlated with the risk of poor prognosis,while CD3+,CD4+,CD4+/CD8+and CD16+/CD56+were negatively correlated with the risk of poor prognosis(P＜0.05).Individual detection of CD3+,CD4+,CD8+,CD4+/CD8+,CD19+,CD16+/CD56+,IL-6 and the combined detection of the seven indicators had certain predictive value for the occurrence of poor prognosis in patients[area under the curve(AUC)＞0.7].Conclusion Plasma T cell subsets and serum IL-6 levels are important factors influencing the prognosis of children with MPP and are independently related to the CT imaging characteristics.

Objective Summarize the endocrine characteristics of 5 children with Wiedemann-Steiner syndrome(WDSTS)to enhance the early recognition capability of clinicians for this condition.Methods A retrospective analysis of the medical history,clinical manifestations,genetic testing,and treatment of 5 children with Wiedemann-Steiner syndrome treated in the endocrinology department of capital center for children's health,capital medical university from October 2020 to December 2024,summarizing the clinical characteristics of the disease.Results Among the 5 cases of WDSTS,there were 2 males and 3 females,with ages ranging from 1.9 to 10 years at the time of diagnosis.Cases 1 and 3 were born prematurely,and cases 1,2 and 5 were diagnosed as small for gestational age(SGA)infants.All 5 children exhibited distinctive facial features,hirsutism,sacral dimple,developmental delay,and adenoid hypertrophy,premature tooth replacement,feeding difficulties,and a high incidence of urinary system abnormalities.Four children complained of slow growth.Cases 1 and 4 were diagnosed with short stature.Cases 3 and 5 had normal height but were slightly shorter with advanced bone age.Case 5 also experienced early puberty.Case 2 was diagnosed with premature adrenarche and idiopathic central precocious puberty due to the presence of pubic hair and breast enlargement.Cases 1 and 3 were treated with recombinant human growth hormone(rhGH),which resulted in significant height growth(approximately 10 cm/year).However,treatment was discontinued in Case 1 due to a significant advancement in bone age.Conclusions WDSTS should be considered in patients presenting with short stature,distinctive facial features,hirsutism,developmental delay,and multiple system deformities.While rhGH treatment can help improve height in these patients,the potential for accelerated bone age maturation during treatment requires careful monitoring.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.