OBJECTIVE: To summarize the clinical and genetic characteristics of children with Silver-Russell syndrome (SRS) and improve the recognition of this disease. METHODS: A retrospective analysis was conducted on the clinical manifestations and genetic testing results of 29 children with SRS diagnosed at the Children's Hospital Affiliated to Zhengzhou University between March 2016 and June 2025. RESULTS: The 29 children had included 18 boys and 11 girls, with the age ranging from 2 months to 16 years. Their primary clinical manifestations included postnatal growth retardation (100%), small for gestational age (SGA) (100%), characteristic facial features (90%), limb asymmetry (83%), feeding difficulties (76%), ulnar deviation of the fifth finger (69%), body mass index (BMI) of < -2 SD (62%), and abnormal bone age (55%), including 15 cases with delayed bone age for an average of 1.5 years and 1 case with advanced bone age for 2.5 years. Additional manifestations included abnormal sexual development in 11 cases (38%), dental malocclusion in 11 cases (38%), allergic diseases in 10 cases (34%), cardiac diseases in 9 cases (31%), skeletal abnormalities in 7 cases (24%), renal hypoplasia in 5 cases (17%), and abnormal cranial MRI findings in 5 cases (17%). Twenty children were treated with recombinant human growth hormone (rhGH) at a dose of 0.1 ~ 0.15 U/(kg.d). Among them, 7 cases achieved annual height increase of ≥ 10 cm, 11 cases achieved annual height increase of ≥ 5 ~ 9 cm, and 2 cases achieved annual height increase < 5 cm. Twenty three children exhibited hypomethylation of imprinted genes in the chromosome region of 11p15, 4 presented maternal uniparental disomy of chromosome 7 [UPD(7)mat], and 2 had harbored nonsense variants of the HMGA2 gene. CONCLUSION SRS patients may present with diverse clinical manifestations including postnatal growth retardation, SGA, characteristic facial features, limb asymmetry, feeding difficulties, and ulnar deviation of the fifth finger. Most patients may exhibit abnormal methylation in the 11p15 region. rhGH therapy can improve the height of these patients.
Humans ; Silver-Russell Syndrome/diagnosis* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Retrospective Studies

Objective:To analyze the clinical efficacy and safety of carglumic acid in the treatment of neonatal hyperammonemia caused by organic acidemia.Methods:A case summary was made.Six cases of neonatal hyperammonemia caused by organic acidemia treated at the Neonatal Intensive Care Unit of Henan Children′s Hospital from March to September in 2024 were included.They received comprehensive ammonia-lowering treatment in combination with oral carglumic acid dispersible tablets.The clinical data of the children were collected and analyzed retrospectively.Changes in blood ammonia levels, blood gas parameters, and complete blood count before and after treatment with carglumic acid were analyzed using the Wilcoxon test.The incidence of adverse reactions and clinical regression during the treatment with carglumic acid was observed.Results:There were 2 females and 4 males in the 6 patients included.Four children suffered from isolated methylmalonic acidemia caused by MUT gene mutations, and the other 2 had propionic acidemia.The clinical manifestations were poor breastfeeding in 6 cases, vomiting in 2 cases, poor response in 6 cases, weight loss in 6 cases, and convulsions in 3 cases.Acute metabolic decompensation abnormalities were presented in all children, such as metabolic acidosis, hyperammonemia, leukopenia and thrombocytopenia.The first dose of carglumic acid was 62-255 mg/kg, the second dose was 75-172 mg/kg.The blood ammonia level decreased from 411.7 (339.7, 623.8) μmol/L before treatment to 108.1 (35.5, 229.1) μmol/L after 48 hours of treatment, showing a statistically significant reduction ( Z=2.20, P<0.05).Three cases with a blood ammonia level higher than 400 μmol/L, it was effectively reduced after treatment with carglumic acid.Two cases did not undergo hemodialysis or peritoneal dialysis.One case underwent hemodialysis but died after withdrawing the treatment.After administration of carglumic acid, metabolic acidosis was corrected in all children, and 2 patients ultimately died after discontinuing the treatment.No causal relationship was identified between adverse events and carglumic acid treatment.The examinations at discharge and during the follow-up period (2-7 months) showed that most laboratory abnormalities (including leukopenia, anemia, thrombocytopenia, hyperlactatemia, hyponatremia, hyperkalemia, elevated myocardial enzymes, and hyperbilirubinemia) returned to normal. Conclusions:Carglumic acid can effectively reduce neonatal hyperammonemia caused by organic academia, improve metabolic disorders, and reduce the need for blood purification or peritoneal dialysis, with good safety.

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

Objective To assess the expression of CXCL8 in cervical cancer and its association with clinicopathological features and therapeutic efficacy of patients.Methods Bioinformatic analysis was performed using The Cancer Genome Atlas and Genotype-Tissue Expression databases to compare CXCL8 expression between cervical cancer and normal tissues.R software(version 4.4.0)was used for data analysis,with the timeROC package applied to construct time-dependent receiver operating characteristic(ROC)curves for evalua-ting the prognostic predictive efficacy of CXCL8.The survival package with the survfit function was used to compare survival differences between CXCL8 high-and low-expression groups.Clinical data and tissue specimens were collected from 94 patients with cervical squa-mous cell cancer treated at The First Affiliated Hospital of Xinjiang Medical University between January 2017 and December 2021.Immu-nohistochemical staining was used to detect CXCL8 expression levels and analyze its correlation with clinicopathological characteristics,therapeutic efficacy,and prognosis.Results Bioinformatic analysis showed that CXCL8 was highly expressed in cervical cancer tissues than in normal tissues(P＜0.05).Time-dependent ROC curves and survival analyses showed that patients with high CXCL8 expression had significantly shorter overall survival than those with low CXCL8 expression(P＜0.001).Immunohistochemical results showed that CXCL8 expression in cervical cancer tissues was significantly higher than that in adjacent tissues(P＜0.000 1).Clinical correlation analy-sis revealed that CXCL8 expression levels were associated with treatment regimen(P＜0.001)and short-term therapeutic efficacy(P=0.017).Compared to the low-expression group,the high-expression group showed a significantly lower therapeutic efficacy and shorter overall survival(P＜0.05).Conclusion CXCL8 is highly expressed in cervical cancer tissues,and patients with high CXCL8 expression have poor prognosis.Thus,CXCL8 may be an effective target for assessing the prognosis and clinical treatment of cervical cancer.

Objective To assess the expression of CXCL8 in cervical cancer and its association with clinicopathological features and therapeutic efficacy of patients.Methods Bioinformatic analysis was performed using The Cancer Genome Atlas and Genotype-Tissue Expression databases to compare CXCL8 expression between cervical cancer and normal tissues.R software(version 4.4.0)was used for data analysis,with the timeROC package applied to construct time-dependent receiver operating characteristic(ROC)curves for evalua-ting the prognostic predictive efficacy of CXCL8.The survival package with the survfit function was used to compare survival differences between CXCL8 high-and low-expression groups.Clinical data and tissue specimens were collected from 94 patients with cervical squa-mous cell cancer treated at The First Affiliated Hospital of Xinjiang Medical University between January 2017 and December 2021.Immu-nohistochemical staining was used to detect CXCL8 expression levels and analyze its correlation with clinicopathological characteristics,therapeutic efficacy,and prognosis.Results Bioinformatic analysis showed that CXCL8 was highly expressed in cervical cancer tissues than in normal tissues(P＜0.05).Time-dependent ROC curves and survival analyses showed that patients with high CXCL8 expression had significantly shorter overall survival than those with low CXCL8 expression(P＜0.001).Immunohistochemical results showed that CXCL8 expression in cervical cancer tissues was significantly higher than that in adjacent tissues(P＜0.000 1).Clinical correlation analy-sis revealed that CXCL8 expression levels were associated with treatment regimen(P＜0.001)and short-term therapeutic efficacy(P=0.017).Compared to the low-expression group,the high-expression group showed a significantly lower therapeutic efficacy and shorter overall survival(P＜0.05).Conclusion CXCL8 is highly expressed in cervical cancer tissues,and patients with high CXCL8 expression have poor prognosis.Thus,CXCL8 may be an effective target for assessing the prognosis and clinical treatment of cervical cancer.

OBJECTIVE: To explore the clinical features of a child with Lamb-Shaffer syndrome (LAMSHF) due to a variant of SOX5 gene. METHODS: A child who was admitted to Children's Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing (WES) was carried out on peripheral blood samples from the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-100). RESULTS: The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c.1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_supporting). CONCLUSION The c.1828_1829insGACT (p.Y610fs*1) variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child. For children with delayed mental, language, intellectual, and motor development, genetic testing should be conducted to facilitate early diagnosis. Above finding has enriched the mutational spectrum of the SOX5 gene.
Humans ; SOXD Transcription Factors/genetics* ; Male ; Infant ; Exome Sequencing ; Genetic Testing ; Mutation

OBJECTIVE: To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. METHODS: A child diagnosed with 3MS type 1 at the Children's Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020). RESULTS: The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. WES revealed compound heterozygous variants in the CUL7 gene: c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child's father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c.2686G>T (p.E896) was classified as a pathogenic (PVS1+PM2_Supporting+PM3), and c.1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+PM2_Supporting). Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). CONCLUSION The compound heterozygous variants c.2686G>T (p.E896*) and c.1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.
Humans ; Cullin Proteins/genetics* ; Female ; Child ; Limb Deformities, Congenital/genetics* ; Exome Sequencing ; Mutation ; Child, Preschool ; Dwarfism ; Muscle Hypotonia ; Spine/abnormalities*

Objective:To explore the clinical features of a child with Lamb-Shaffer syndrome (LAMSHF) due to a variant of SOX5 gene. Methods:A child who was admitted to Children′s Hospital Affiliated to Zhengzhou University in July 2022 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing (WES) was carried out on peripheral blood samples from the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-100).Results:The child, an one-year-and-seven-month-old male, has manifested delayed development in speech and language, intelligence and movement, in addition with mild facial deformities and eye signs. Whole exome sequencing revealed that he has harbored a heterozygous c. 1828_1829insGACT (p.Y610fs*1) frameshifting variant of the SOX5 gene. Sanger sequencing confirmed the variant to be de novo in origin. The variant was also unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+ PS2+ PM2_supporting). Conclusion:The c. 1828_1829insGACT (p.Y610fs*1) variant of the SOX5 gene probably underlay the pathogenesis of LAMSHF in this child. For children with delayed mental, language, intellectual, and motor development, genetic testing should be conducted to facilitate early diagnosis. Above finding has enriched the mutational spectrum of the SOX5 gene.

Objective:To explore the clinical features, genetic characteristics in a child with Miller-McKusick-Malvaux syndrome (3MS) type 1 caused by CUL7 gene variant. Methods:A child diagnosed with 3MS type 1 at the Children′s Hospital Affiliated to Zhengzhou University in February 2021 was selected as the subject of this study. Peripheral blood samples were collected from the child and her parents for genomic DNA extraction. Whole exome sequencing (WES) was performed on the child, and Sanger sequencing was used to validate the candidate variants and analyze their pathogenicity. A literature search was conducted using the keywords "3M syndrome" in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed databases from inception to December 2024. The clinical data of Chinese children with 3MS reported in the literature were summarized. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-K-020).Results:①The child was a 6-year-old and 2-month-old female with facial dysmorphism, skeletal abnormalities, and growth and developmental delay. ②WES revealed compound heterozygous variants in the CUL7 gene: c. 2686G>T (p.E896*) and c. 1200delT (p.R401Gfs66). Sanger sequencing confirmed that these two variants were inherited from the child′s father and mother, respectively. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, c. 2686G>T (p.E896) was classified as a pathogenic (PVS1+ PM2_Supporting+ PM3), and c. 1200delT (p.R401Gfs*66) was classified as a likely pathogenic (PVS1+ PM2_Supporting). ③ Based on the literature search strategy, 18 relevant articles were identified, including a total of 32 Chinese cases of 3MS, of which 8 were fetuses. A total of 32 Chinese 3MS cases were included in the literature review, of which 8 were fetuses. The majority of these cases carried variants in the CUL7 gene (20/32, 62.5%) and OBSL1 gene (12/32, 37.5%). The main clinical manifestations included intrauterine or postnatal growth and developmental delay (32/32, 100.0%), triangular facies (27/32, 84.3%), and skeletal abnormalities (21/32, 65.6%). Conclusion:The compound heterozygous variants c.2686G>T (p.E896*) and c. 1200delT (p.R401Gfs*66) in the CUL7 gene are likely the genetic cause of 3MS type 1 in the child. For children presenting with facial dysmorphism, skeletal abnormalities, and intrauterine or postnatal growth and developmental delay, 3MS should be considered as a differential diagnosis.

Objective:To analyze the genetic characteristics of clinical manifestations in children with KBG syndrome due to microdeletions.Methods:A retrospective case summary was conducted. Four children diagnosed with KBG syndrome due to 16q24.3 microdeletion at Children′s Hospital of Zhengzhou University from July 2021 to April 2024 were enrolled.Their clinical manifestations, biochemical parameters, imaging data, whole-exome sequencing results, treatments and follow-up outcomes were reviewed.Results:The cohort included two males and two females (diagnosed at 81, 18, 26, and 56 months of age, respectively), from four unrelated families. All patients exhibited peculiar facial features (Cupid′s bowed-shaped lips, prominent ears, thick eyebrows), skeletal abnormalities (brachydactyly, abnormal ribs, short stature, etc.), ocular anomalies (astigmatism, strabismus, amblyopia, etc.), intrauterine growth restriction, and developmental retardation. Case 2, 3, 4 had cranial imaging abnormalities, including thin anterior pituitary lobes with pineal cyst, left ventricular cyst, and abnormal pituitary stalk or lateral ventricles with sinusitis, respectively. Two children had intellectual disability, two had congenital heart disease, and one had delayed bone age and hair abnormalities. Whole exome genomic sequencing confirmed 16q24.3 microdeletions encompassing ANKRD11 gene in all four cases. Two children treated with recombinant human growth hormone achieved height increments of 1.5 s and 0.4 s, respectively. Conclusions:Typical features of 16q24.3 microdeletion-induced KBG syndrome include peculiar facial features, macrodontia, skeletal anomalies, neurological abnormalities, and ocular defects. Genetic testing is essential for definitive diagnosis. The treatment of KBG syndrome requires early diagnosis and multidisciplinary collaboration to implement individualized treatment for multisystem symptoms.