Objective:To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. Methods:A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children′s Hospital Affiliated to Zhengzhou University in March 2023 due to " inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.2022-K-L025). Results:The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c. 240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+ PM2_Supporting+ PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. Conclusion:The frameshift variation of TRAPPC6B gene c. 240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provid basis for genetic counseling and prenatal diagnosis of this family.

Objective:To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. Methods:A child presented at the Affiliated Children′s Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child′s clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001).Results:The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c. 790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. Conclusion:The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c. 790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.

Paraganglioma（PGL）is an extra-adrenal catecholamine-secreting endocrine tumor. We reported a young female patient who was admitted to the hospital with right flank pain and diagnosed with right retroperitoneal PGL with Mayo Ⅳ inferior vena cava tumor thrombus（double tumor thrombus）. After multidisciplinary consultation，right retroperitoneal PGL resection，right nephrectomy，inferior vena cava Mayo Ⅳ tumor thrombus resection and reconstruction were performed. Postoperative pathology showed that the primary tumor and inferior vena cava tumor thrombus was consistent with PGL. Genetic testing revealed a heterozygous germline nonsense mutation at c.69_70delinsTT（p.Q24*）locus of the SDHB gene in the patient. His mother was a carrier of the gene，but his father and sister did not carry the mutation. The patient recovered smoothly after surgery.

Background and Aims:Medullary thyroid carcinoma(MTC)is an aggressive malignancy that is frequently associated with cervical lymph node metastasis,significantly affecting patient prognosis.However,the risk factors for lateral cervical lymph node metastasis(LLNM)in MTC remain inconclusive.This study aims to identify the risk factors associated with LLNM in MTC patients,in order to inform individualized surgical decision-making.Methods:The clinicopathologic data of 242 patients with MTC who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from 2011 to 2019 were retrospectively collected.The relationships between preoperative tumor markers,including calcitonin and carcinoembryonic antigen(CEA),and LLNM were evaluated.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for LLNM.Results:Preoperative calcitonin level was significantly associated with tumor diameter,the number of lymph node metastases,and the extent of lymph node involvement,while preoperative CEA level was significantly associated with tumor diameter(all P<0.05).The area under the ROC curve for preoperative calcitonin in diagnosing LLNM was 0.750(P=0.000),with an optimal cutoff value of 266.00 ng/L(sensitivity 0.854,specificity 0.577).The diagnostic value of preoperative CEA for LLNM was limited.Univariate analysis showed that sex,extracapsular extension,T stage,central lymph node metastasis(CLNM),bilateral lesions,preoperative calcitonin,tumor diameter,and multifocality were significantly associated with LLNM in MTC patients(all P<0.05).Multivariate analysis revealed that CLNM(OR=17.645,95%CI=7.728-40.290)and preoperative calcitonin≥266.00 ng/L(OR=7.832,95%CI=3.132-19.582)were independent risk factors for LLNM.Conclusion:CLNM and elevated preoperative calcitonin level are closely associated with LLNM in patients with MTC.The combination of these two indicators may help identify high-risk patients for LLNM,thereby and promoting individualized and precise treatment strategies for MTC.

Objectives:To investigate the clinical efficacy of the distal tension-offloading cosmetic suture technique in reducing hypertrophic scar formation following open thyroidectomy.Methods:Clinical data and postoperative incision appearance of 138 patients undergoing open thyroidectomy at the Department of Thyroid and Neck Oncology of Tianjin Medical University Cancer Institute and Hospital, as well as the Department of Head and Neck Oncology of Tianjin Cancer Hospital Airport Hospital, from Aug 2023 to Jan 2024 was enrolled. Patients were devided into two groups based on the incision closure method: the distal tension-offloading cosmetic suture group (tension reduction group, 37 cases) and ordinary intradermal suture group (control group A, 55 cases evaluated 3 months post-surgery; control group B, 46 cases evaluated 6 months post-surgery). The Vancouver Scar Scale (VSS) was employed to assess the appearance of the wounds at 3 and 6 months post-surgery .Results:On 3 and 6 months post-surgery, the total VSS scores for patients in the tension reduction group were 2.8 ± 2.3 and 2.5 ± 2.5, respectively,while that in control group A on 3 months was 5.2 ± 3.0, and in group B on 6 months was 5.3 ± 3.4. The differences were statistically significant (all P<0.001). On 3 and 6 months post-surgery, the proportions of hypertrophic scars in the tension reduction group were 14% (5/37) and 11% (4/37), respectively , while in control group A it was 35% (19/55) , and in control group B was 35% (16/46) at 6 months, with differences being statistically significant ( P=0.024, 0.011 ). On 6 months post-surgery, 51 % (19/37) of patients in the tension reduction group achieved 'socially invisible aesthetic incisions', while only 15% (7/46) of patients in control group B achieved the same outcome ( P<0.01). Conclusion:Distal tension-offloading cosmetic suture significantly reduces the incidence of incision hypertrophic scars in open thyroid surgery.

Objective To compare the effects of main artery clamping(MAC)and selective artery clamping(SAC)strategies on postoperative renal function in patients with chronic renal insufficiency undergoing robot-assisted partial nephrectomy.Methods A retrospective cohort study was conducted on 231 patients with preoperative chronic renal insufficiency[eGFR<90 mL/(min·1.73 m2)with renal injury markers or eGFR<60 mL/(min·1.73 m2)]who underwent robot-assisted partial nephrectomy in the Department of Urology of the First Affiliated Hospital of Army Medical University from February 2018 to February 2024.According to intraoperative renal artery clamping strategy,they were divided into a MAC group(n=129)and a SAC group(n=102).Preoperatively,individualized renal artery clamping strategies were developed using a machine learning-based multimodal holographic 3-D reconstruction technique.Serum creatinine(Scr)level was measured at 3 d and 3 months after surgery,and estimated glomerular filtration rate(eGFR)was calculated using the chronic kidney disease epidemiology collaboration equation(CKD-EPI)formula.Renal dynamic imaging with 99mTc-DTPA or 99mTc-MAG3 was used to assess the GFR of the affected kidney.Results At 3 d after surgery,the decrease in GFR of the affected kidney was significantly lower[(8.3±7.7)vs(16.0±10.2)mL/(min·1.73 m2),95%CI:-10.2～-5.2,P<0.001]in the SAC group than the MAC group.Scr increment analysis showed that the SAC group exhibited notably lower Scr increase[8.2(2.5,18.7)vs 15.5(5.8,28.3)μmol/L,95%CI:-12.3～-1.8,P=0.027],and milder eGFR decline[3.0(0.5,7.8)vs 7.5(2.0,14.3)mL/(min·1.73 m2),95%CI:-6.2～-0.8,P=0.015].And,in 3 months after surgery,the SAC group had lower Scr level[(89.2±23.1)vs(95.3±22.1)μmol/L,95%CI:-11.9～-0.3,P=0.042],and higher GFR of the affected kidney[(33.5±10.5)vs(26.1±10.9)mL/(min·1.73 m2),95%CI:4.6～10.2,P<0.001].Conclusion For patients with chronic renal insufficiency undergoing robot-assisted partial nephrectomy,SAC strategy is superior to MAC strategy in protecting postoperative renal function without increasing surgical risk.

Objective To investigate the effects of Jiawei Ditan Decoction on neurological function,pentraxin-3(PTX-3),and vascular endothelial growth factor(VEGF)in patients with post-ischemic stroke cognitive impairment(PSCI).Methods A total of 97 patients with PSCI who were admitted to Xuzhou Central Hospital from March 2022 to March 2024 were enrolled and randomly assigned to control group(n=48)or decoction group(n=49)using the envelope drawing method.The control group received conventional treatment,while the decoction group was additionally treated with Jiawei Ditan Decoction.Clinical efficacy,Traditional Chinese Medicine(TCM)syndrome scores,cognitive and functional assessments,laboratory markers,and oxidative stress levels were compared between the two groups.Results The total effective rate in the decoction group was significantly higher than that in the control group(P<0.05).At 3 and 6 months after treatment,TCM syndrome scores in the decoction group were lower than those in the control group(P<0.05).The scores of the Montreal cognitive assessment(MoCA),mini-mental state examination(MMSE),and Barthel index(BI)in the decoction group were higher than those in the control group at 3 months after treatment,while the National Institutes of Health stroke scale(NIHSS)score in the decoction group was lower than that in the control group(P<0.05).At 1 month after treatment,PTX-3 and hypersensitive C-reactive protein(hs-CRP)levels in the decoction group were lower than those in the control group,while VEGF,superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and nitric oxide(NO)levels in the decoction group were higher than those in the control group(P<0.05).Conclusion Jiawei Ditan Decoction exhibits significant effects on improving neurological function and modulating PTX-3 and VEGF levels in patients with PSCI.

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 phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. METHODS: A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children's Hospital Affiliated to Zhengzhou University in March 2023 due to "inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethic No.2022-K-L025). RESULTS: The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c.240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+PM2_Supporting+PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. CONCLUSION The frameshift variation of TRAPPC6B gene c.240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provide basis for genetic counseling and prenatal diagnosis of this family.
Humans ; Infant ; Male ; Frameshift Mutation ; Homozygote ; Neurodevelopmental Disorders/genetics* ; Phenotype

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Osteopathia striata with cranial sclerosis (OSCS) due to variant of AMER1 gene. METHODS: A child presented at the Affiliated Children's Hospital of Zhengzhou University in July 2024 due to growth and development retardation was selected as the study subject. A retrospective study was conducted to collect the child's clinical data. Peripheral blood samples (2 mL each) were collected from the child and her parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used for the verification of candidate variants. The pathogenicity of variant was rated according to the guidelines from American College of Medical Genetics and Genomics (ACMG). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethics No.: 2024-108-001). RESULTS: The patient, a 4-year-and-10-month-old girl, presented with global developmental delay, short stature, cleft palate, distinct facial features, and hearing impairment. WES revealed that she has harbored a heterozygous c.790_794dup (p.Cys265Trpfs*19) variant of the AMER1 gene, which was not detected in either parent. Based on the guidelines from ACMG, the gene variant was classified as pathogenic (PVS1 + PS2 + PM2_supporting). As the result of a non-triplet base insertion in the coding region of the AMER1 gene, it has converted a codon originally encoding an amino acid into a stop codon, and led to a truncated protein, causing severe alteration and dysfunction of the protein. CONCLUSION The child was diagnosed with OSCS for clinical features such as global developmental delay, short stature, cleft palate, distinctive facial features, and hearing impairment, for which the de novo heterozygous frameshift variant AMER1: c.790_794dup (p.Cys265Trpfs*19) may be accountable. Above finding has expanded the mutational spectrum of OSCS and provided a basis for genetic counseling and prenatal diagnosis for the family.
Humans ; Female ; Child, Preschool ; Osteosclerosis/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Mutation ; Exome Sequencing ; Retrospective Studies ; Tumor Suppressor Proteins