Objective:To analyze the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Hereditary antithrombin deficiency.Methods:A pedigree diagnosed at the the Second Affiliated Hospital of Wenzhou Medical University, Yuying Children’s Hospital in June, 2020 was selected as the study subject. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), and thrombin time (TT) of the probands and their pedigree members were determined using a STA-R automatic coagulation analyzer. Antithrombin activity (AT: A) and antithrombin antigen (AT: Ag) in plasma were determined with chromogenic substrate and immunonephelometry assays. All exons and flanking sequences of the anticoagulant protein gene SERPINC1 were amplified by PCR and subjected to Sanger sequencing. Candidate variants were verified with bioinformatic tools (PolyPhen-2, SIFT, Mutation Taster and PYMOL) to explore their effect on the function and structural conformation of the protein. Results:The probands (Ⅱ 2, Ⅱ 10), their brother (Ⅱ 5) and sons (Ⅲ 1, Ⅲ 8) had shown normal PT, APTT, FIB, and TT, but significantly decreased AT: A and AT: Ag, with their levels being 34%, 57%, 56%, 48%, 53% and 13.51 mg/dL, 13.44 mg/dL, 18.39 mg/dL, 17.36 mg/dL, 17.71 mg/dL, respectively. The remaining pedigree members had normal values. Sanger sequencing revealed that the probands and all affected pedigree members had harbored a heterozygous c. 851T>C (p.Met284Thr) missense variant in exon 5 of the SERPINC1 gene. Bioinformatic analysis and simulation suggested that the variant has resulted in alteration of hydrogen bonds at the c. 851 position, which may affect the structure of the protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS1+ PM1+ PM5+ PP1+ PP4). Conclusion:The probands and other affected members were all diagnosed with type I hereditary AT deficiency, for which the c. 851 T>C (p.Met284Thr) variant of the SERPINC1 gene may be accountable.

As a new hypoglycemic drug,Dapagliflozin has attracted much attention because of its unique hypoglycemic mechanism. It has been used in many studies on type 2 diabetes mellitus,but the application of type 1 diabetes mellitus(T1DM)in the eastern population is rare. This article uses Dapagliflozin through a case of obese T1DM to provide new ideas for the treatment of T1DM.

This article reports a case of ROHHAD syndrome with elevated D-dimer levels and reviews the literature to summarize the clinical characteristics of this disease.A 9 years and 9 months old boy was treated at the Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University in July 2020, he was evaluated for rapid-onset obesity but poor height growth since he was 3 years old.He also presented with unstable temperature, frequent diarrhea and hypogonadism.The laboratory findings revealed hypernatremia, hyperprolactinemia and elevated partial pressure of carbon dioxide.The pathological finding suggested the left adrenal ganglioneuroma.Polysomnography data showed central hypoventilation with obstructive sleep apnea.The boy was finally diagnosed with ROHHAD syndrome.It was the first report of the ROHHADNET case in China.The boy had a high level of D-dimer before surgery, but it fell to normal following the surgical excision of the adrenal tumor.ROHHAD syndrome patients may be at risk of thrombosis.Changes in D-dimer level may be used as a marker to help predict the tumor progression in ROHHADNET.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

To report a case of fructose-1, 6-bisphosphatase deficiency child with delayed diagnosis for seven years, and review the literature. A 13-year-old boy presented with recurrent episodes of hypoglycemia after infection since 6 years old, he also had convulsion and short stature. The laboratory finding revealed ketotic hypoglycemia, lactic acidosis, transient elevated ALT and UA. The genetic analysis showed compound heterozygous mutations of c. 960-961insG and c. 355G> A in FBP1 gene. Among eighteen patients reported in China, 88.9% had convulsion, 16.7% had growth retardation, the average delayed diagnosis spent 2.8 years, which could result in permanent brain damage and high death risk. The most common mutation was c. 960-961insG, followed by c. 355G>A and c. 490G>A, these mutations maybe hot spot sites of FBPl gene in China.

OBJECTIVE: To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency. METHODS: All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster). RESULTS: The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic. CONCLUSION The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.
Antithrombin III/genetics* ; Antithrombin III Deficiency/genetics* ; DNA Mutational Analysis ; Genetic Testing ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with inherited afibrinogenemia. METHODS: For the proband and his family members, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrin(ogen) degradation products (FDPs), D-dimer (D-D), plasminogen activity (PLG:A) and the TT mixed experiment with protamine sulfate were determined with a STAGO-R automatic coagulation analyzer. The activity and antigen of fibrinogen (Fg) in plasma were measured with the Clauss method and immunonephelometry method, respectively. All exons and flanking regions of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR and directly sequenced. Human Splicing Finder software was used to predict and score the change of splicing site caused by the mutation. RESULTS: The proband showed normal FDPs and D-D but significantly prolonged TT, PT and APTT. The activity and antigen of fibrinogen in plasma were significantly decreased (<0.1 g/L). His young sister and parents showed slightly prolonged TT (18.20-18.50 s) and decreased fibrinogen activity (1.27-1.54 g/L) and fibrinogen antigenic content (1.34-1.56 g/L). Genetic testing revealed that the proband has carried homozygous IVS7-12A>G (g.4147A>G) mutations of the FGG gene, for which his parents and young sister were heterozygous. As predicted by Human Splicing Finder and Mutation Taster software, the variant may generate a new splicing site which can extend the sequence of exon 7 by 11 bp, with alteration of the coding sequence. PROVEAN suggested the variant to be deleterious. CONCLUSION The afibrinogenemia of the proband may be attributed to the FGG IVS7-12A>G variant, which was unreported previously.
Adult ; Afibrinogenemia/genetics* ; Female ; Fibrinogen/genetics* ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree

Objective: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. Methods: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. Results: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c. 92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. Conclusion The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.

OBJECTIVE: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. METHODS: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. RESULTS: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. CONCLUSION The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.
Afibrinogenemia ; congenital ; genetics ; DNA Mutational Analysis ; Female ; Fibrinogen ; genetics ; Humans ; Mutation ; Pedigree ; Phenotype

OBJECTIVE: To carry out phenotypic and genotypic analysis for two Chinese pedigrees affected with coagulation factor XII (F XII) deficiency. METHODS: Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), and blood coagulation factor VIII, IX, XI, XII activity (FVIII:C, FIX:C, FXI:C, FXII:C) were determined with one stage clotting assay on a STAGO coagulation analyzer. FXII antigen was determined with an enzyme linked immunosorbent assay (ELISA). The 14 exons and their flanking sequences of the F12 gene were subjected to PCR amplification and Sanger sequencing. The conservation and structure of mutant protein were analyzed with MegAlign software and PYMOL software. RESULTS: The APTT of the probands was significantly prolonged, while their FXII:C and FXII:Ag were significantly reduced. Genetic analysis of the proband has revealed three novel mutations in the F12 gene, including g.5972G>A splice site mutation in intron 5, g.8810_8814delGTCTA in exon 14, and g.6259G>A (p.Pro182Leu) in exon 7. In addition, a previously known mutation IVS13-1G>A has been found. CONCLUSION Four mutations have been identified in the two Chinese pedigrees, among which three were novel. Above mutations probably played a role in the defect of FXII in the two pedigrees.
Exons ; Factor XII ; genetics ; Factor XII Deficiency ; genetics ; Genetic Testing ; Humans ; Pedigree