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
<p><b>OBJECTIVE</b>To investigate the presence of p53 gene deletion in Xinjiang patients with chronic lymphocytic leukemia and its clinical significance.</p><p><b>METHODS</b>Interphase fluorescence in situ hybridization (FISH) was used to detect the p53 gene deletion in 77 patients with CLL. Presence of the deletion and its association with clinical and laboratory features as well as prognostic factors were analyzed. Kaplan-Meier method was used to calculate survivals, and the results were compared using a Log-rank test.</p><p><b>RESULTS</b>p53 gene deletion was found in 10 (12.9%) of the patients but none from the control group (P<0.05). The deletion was found in 12.5% (4/32) of ethnic Hans and 13.3% (6/45) of ethnic Uyghurs (P>0.05). No significant different distribution of p53 gene deletion was found in regard to sex, age, ethnicity, peripheral blood cell count (except for Hb) or the levels of lactate dehydrogenase, β2-micro globulin and CD38 (P>0.05). The deletion rate was higher in the group with high expression of ZAP-70 and patients with advanced stage disease than that in the group of low expression and early-stage CLL (P<0.05). Among 20 patients who received fludarabine therapy, the overall remission rate for those with p53 gene deletion (20%) was lower than those without (75%) (P<0.05). With a median follow-up time of 39.0 (8.0-136.0) months, 11 cases had died (14.3%), among them, 7 cases died from CLL and related complications, and all of them were founded p53 gene deletion. In patients with p53 gene deletion, the progression-free survival (18 months) was shorter than those without the deletion (55 months) (P<0.05).</p><p><b>CONCLUSION</b>The p53 gene deletion has been found in more than 10% of patients with CLL, and the deletion rate did not significantly differ between ethnic Han and Uyghur patients. The deletion is associated with advanced stage of the disease. High-level ZAP-70 expression and the presence of p53 deletion are associated with shorter survival and poor response to fludarabine containing therapy. Therefore, drugs affecting the p53 signaling pathway should be avoided.</p>