Genetic analysis of a Chinese pedigree affected with Congenital coagulation factor XII deficiency due to a c.1A>G start codon variant of F12 gene / 中华医学遗传学杂志

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.

Research progress in the diagnosis and treatment of ankylosing spondylitis combined with spinal fracture / 中华创伤杂志

The spinal fracture in patients with ankylosing spondylitis (AS) is predominantly unstable, involving all three columns of the spine. If AS combined with spinal fracture is not effectively treated in the early stage, continuous stress on the lesion site may result in pseudarthrosis, progressive kyphotic deformity, neurologic deficits and other complications during later stages. Currently, the diagnosis of AS combined with spinal fracture mainly relies on symptoms, signs and imaging examination. However, there is a certain rate of missed diagnoses. Although surgical intervention is preferred, there is no unified standard for selecting the surgical approaches. Anterior cervical surgery, due to potential risks of unstable fixation and vascular nerve damage, is limited to a selected group of AS patients combined with concurrent cervical spine fracture. The combined anterior and posterior approach provides good stability, but patients may not tolerate the surgical trauma. The traditional posterior open surgery is widely employed and can achieve good results, but it also causes significant surgical trauma and intraoperative bleeding. Minimally invasive posterior percutaneous procedures are becoming more and more popular due to its advantages of less trauma, less bleeding and faster recovery. Additionally, the use of robot-assisted and navigation techniques increases both safety and accuracy during operations. In this study, the authors reviewed the progress in the diagnosis and treatment of AS combined with spinal fracture, providing references for optimizing diagnostic and therapeutic strategies.