RESUMO
【Objective】 To retrospectively analyze the clinical manifestations, related laboratory examinations and gene mutation of 20 patients with congenital Fibrinogen disorders (CFD) admitted to our hospital from February 2017 to December 2021, so as to improve the understanding of CFD diagnosis. 【Methods】 Clinical characteristics and laboratory examination of 20 CFD patients were collected, and common secondary hypoFibrinemia factors were excluded. Gene sequencing was performed on all exons and flanks of FGA, FGB and FGG genes of 20 patients to find gene mutation sites. The peripheral blood genomic DNA was collected from the family members of two CFD patients, and the genes of the corresponding mutation sites of the proband were detected. 【Results】 The 20 CFD patients had no history of bleeding; 11 female patients had no history of spontaneous abortion; all 20 patients had reduced Fib and prolonged thrombin time (TT). There were 13 gene mutations of different types in 20 patients, among which 90% (18/20) were missense mutations, 5% (1/20) was deletion mutation, and 5% (1/20) was frameshift mutation. Seven patients (35%) had Arg35His mutation at site 104 of the FGA chain, among which 3 new gene mutations have not been reported in China. 【Conclusion】 Most CFD patients with mild or asymptomatic symptoms can be diagnosed by genetic testing and screening. FGA chain Arg35His is a mutation hotspot in this region, and all of them are Uyghur. Whether the mutation of this site is related to ethnicity needs to be confirmed by further studies.
RESUMO
【Objective】 To investigate the distribution frequency and characteristics of Rh and Kell erythrocyte blood group antigens in Uygur population in Xinjiang, and to explore the molecular mechanism of K gene positive patients, so as to build a local rare blood group bank and improve the ability of clinical blood security. 【Methods】 From June 2018 to February 2020, blood samples of 4 000 unrelated Uygur healthy individuals from the Medical Examination Center of our hospital and other cooperative hospitals across the autonomous region were selected. Rh and Kell blood group antigens were detected using K/Rh antigen microcolumn gel cards. The exons of Kell gene were amplified by PCR and then subjected to electrophoresis and direct sequencing to investigate the molecular mechanism. 【Results】 In Xinjiang Uygur healthy population, 1) The RhD negative rate was 5.675% (227/4 000), including 5 phenotypes; RhD positive rate was 94.325% (3 773/4 000), including 9 phenotypes, which were in line with Hardy-Weinberg equilibrium distribution. The C/E antigen frequency in RhD negative and positive patients was 13.216%/4.185% vs 52.876%/25.788% (PC, g. 412A>G, exon 6, g. 133C>T, and g. 189T>C, respectively, two of which caused changes in amino acid sequence: alanine at position 193 to methionine (p.Ala193Met) and alanine 423 to valine (p.al423Val). The prediction of RNA secondary structure and protein conformation after mutation using relevant biological information software found that the mutation caused changes in RNA secondary structure, free energy, protein conformation and function. 【Conclusion】 The frequency of RhD antigen negative in Xinjiang Uygur population was higher than that in other ethnic groups, and the distribution of C/E antigen was different in D antigen negative/positive patients. The distribution of K antigen in Kell blood group system was higher than that in other ethnic groups (P<0.05). The primary and secondary structure changes of nascent peptide chain caused by a single point mutation in Kell gene may be one of the molecular mechanisms of K antigen positivity.