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OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a consanguineous Chinese pedigree affected with Congenital coagulation factor XII (XII) deficiency.@*METHODS@#Members of the pedigree who had visited Ruian People's Hospital on July 12, 2021 were selected as the study subjects. Clinical data of the pedigree were reviewed. Peripheral venous blood samples were taken from the subjects. Blood coagulation index and genetic testing were carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#This pedigree has comprised 6 individuals from 3 generations, including the proband, his father, mother, wife, sister and son. The proband was a 51-year-old male with kidney stones. Blood coagulation test showed that his activated partial thromboplastin time (APTT) was significantly prolonged, whilst the FXII activity (FXII:C) and FXII antigen (FXII:Ag) were extremely reduced. The FXII:C and FXII:Ag of proband's father, mother, sister and son have all reduced to about half of the lower limit of reference range. Genetic testing revealed that the proband has harbored homozygous missense variant of c.1A>G (p.Arg2Tyr) of the start codon in exon 1 of the F12 gene. Sanger sequencing confirmed that his father, mother, sister and son were all heterozygous for the variant, whilst his wife was of the wild type. By bioinformatic analysis, the variant has not been included in the HGMD database. Prediction with SIFT online software suggested the variant is harmful. Simulation with Swiss-Pbd Viewer v4.0.1 software suggested that the variant has a great impact on the structure of FXII protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.1A>G (p.Arg2Tyr) variant of the F12 gene probably underlay the Congenital FXII deficiency in this pedigree. Above finding has further expanded the spectrum of F12 gene variants and provided a reference for clinical diagnosis and genetic counseling for this pedigree.
Subject(s)
Male , Female , Humans , Middle Aged , Factor XII/genetics , Pedigree , Codon, Initiator , East Asian People , Mothers , Factor XII Deficiency/genetics , MutationABSTRACT
Objective To assess the clinical utility of measurement of plasma heparin-binding protein (HBP) in diagnosis and prognosis of sepsis.Methods This is a retrospective study on the performance of plasma heparin-binding protein, procalcitonin and C-reaction protein in the early diagnosis of sepsis. Thirty-one patients with sepsis, 16 patients with severe sepsis, 12 patients with septic shock and 37 control patients without confirmed sepsis, all admitted to the Intensive Care Units (ICU) of the Third Hospital Affiliated to Wenzhou Medical University and Wenzhou Central Hospital from August 2014 to November 2016, were enrolled in the study. The plasma level of HBP, procalcitonin (PCT) and C-reactive protein (CRP) were measured, and the detailed clinical data were retrieved from the patient chart records for all patients described above. Comparison of each laboratory and clinical parameters between groups was carried out by Non-parameter Test. The efficiency of each parameter was calculated by receiver operating characteristics curves (ROC) analysis. The correlation between HBP, PCT or CRP and clinical or other laboratory parameters was explored using Spearman correlation analysis.Results HBP was significantly elevated in patients with severe sepsis[(100.65±58.82)ng/ml and(31.86±36.87)ng/ml,Z=-3.856,P<0.05;(100.65±58.82)ng/ml and(24.96±17.49)ng/ml,Z=-3.556,P<0.05]and in patients with septic shock[(148.28±99.73)ng/ml and(31.86±36.87)ng/ml,Z=-4.432,P<0.05;(148.28±99.73)ng/ml and(24.96±17.49)ng/ml,Z=-4.157,P<0.05], respectively, while CRP[(154.64±62.90)mg/L and(92.56±67.49)mg/L,Z=-2.749,P<0.05;(154.64±62.90)mg/L and (79.21±51.80)mg/L,Z=-3.218,P<0.05]and PCT[(32.86±39.93)ng/ml and(2.70±6.24)ng/ml,Z=-3.395,P<0.05;(32.86±39.93)ng/ml and(4.21±14.94)ng/ml,Z=-4.092,P<0.05]were increased only in patients with septic shock (P<0.05).For HBP, the area of under the ROC curves (AUC) was the biggest (AUC=0.687), indicating the clinical significance(P<0.05) with excellent sensitivity(0.729) at the optimal cut-off value(18.58 ng/ml). In addition, HBP(APTT: r=0.244, P=0.016;PT: r=0.351, P<0.001;INR: r=0.314, P=0.002;D-Dimer: r=0.334, P=0.001;lactic acid: r=0.394, P<0.001), CRP(APTT: r=0.271, P=0.008;PT: r=0.348, P=0.001;INR: r=0.264, P=0.009;D-Dimer: r=0.257, P=0.012;lactic acid: r=0.329, P=0.001) and PCT(APTT: r=0.375, P<0.001;PT: r=0.523, P<0.001;INR: r=0.535, P<0.001;D-Dimer: r=0.254, P=0.013;lactic acid: r=0.422, P<0.001)were positively correlated to coagulation function and to lactate.Conclusion HBP could probably be acted as an important biomarker for diagnosis and prognosis for patients with sepsis, esp., for patients with severe sepsis and septic shock.
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Objective To analyze the virulence genes and molecular typing of non-O1/non-O139 Vibio cholerae in bloodstream infection,and to provide the scientific basis for its diagnosis,treatment, prevention and controls.Methods Five Vibio cholerae strains were obtained from blood samples of five inpatients with sepsis in Ruian People ’s Hospital from 2012 to 2015 . Morphological examination, biochemical identification,drug sensitivity test and multilocus sequence typing (MLST)classification analysis of strains were conducted.Totally 17 virulence genes were detected by PCR amplification.Results These five suspected Vibrio cholerae isolates were confirmed as non-O1/non-O139 Vibrio cholerae . Drug susceptibility test showed that all the strains were sensitive to tetracycline,ciprofloxacin,piperacillin and tazobactam, meropenem, amikacin and gentamicin; one strain was resistant to trimethoprim/sulfamethoxazole;all were resistant to ampicillin.MLST analysis showed that all strains were new sequence types (ST),belonging to ST268,ST269,ST267,ST270 and ST271 ,and two novel alleles of RY03(mdh:60 and pyrC:86)were discovered.Virulence genes testing showed that the five strains were divided into 4 virulence genotypes:RY02 and RY04 (hlyA + toxR + hap + rtxA + nanH + vasH + vasA +vasK + ),RY01 (hlyA +toxR +hap +rtxA +nanH +vasH -vasA +vasK - ),RY03 (hlyA +toxR +hap +rtxA +nanH - vasH + vasA + vasK + ) and RY05 (hlyA + toxR + hap + rtxA + nanH + vasH - vasA - vasK - ). Conclusions Non-O1/non-O139 Vibrio cholerae can cause human bloodstream infection in immunocompromised patients.The pathogenic factors may be related to the virulence genes of hlyA, toxR,hap ,rtxA and T6SS.