ORIGINAL ARTICLESPhenotype and genotype analysis of patients with severe factor XI deficiency in Shaanxi Province, ChinaYuan, Lia,b; Chen, Weia; Wang, Xiaoqina; Zhang, HengcAuthor Information aDepartment of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University bMedical College of Xi’an Jiaotong University cDepartment of Clinical Laboratory, Sun Simiao Hospital of Beijing University of Chinese Medicine, Tong chuan, Shaanxi, China Correspondence to Wei Chen, Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China E-mail: [email protected] Received 7 April, 2021 Revised 2 June, 2021 Accepted 22 June, 2021 Blood Coagulation & Fibrinolysis: December 2021 - Volume 32 - Issue 8 - p 539-543 doi: 10.1097/MBC.0000000000001061 Buy Metrics Abstract Congenital coagulation factor XI (FXI) deficiency is a rare bleeding disorder with a heterogeneous haemorrhagic phenotype and various hotspot gene mutations associated with race and geography. Studies on FXI deficiency in Shaanxi Province, China, are scarce. In this study, seven patients with severe FXI deficiency and several family members were analysed. The International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) was applied to assess bleeding symptoms. FXI activity was determined using a one-stage method, and the FXI antigen was measured by enzyme-linked immunosorbent assay. Targeted capture next-generation sequencing and Sanger sequencing were applied to detect FXI gene mutations. The bleeding phenotype varied, although none of the participants had a history of spontaneous bleeding. One maternal received replacement therapy during the perinatal period, one female patient presented with menorrhagia, one male patient experienced severe postoperative bleeding and others were asymptomatic. Family members with heterozygous mutations were all asymptomatic. The FXI activity of all the patients ranged from less than 1 to 3.1 IU/dl, and a synchronous decrease in the FXI antigen was observed. Two missense mutations (p. Gly350Glu and p. Cys482Trp), one nonsense mutation (p. Gln384∗) and one novel frameshift mutation (p. Ser225Phefs∗16) were detected. The bleeding manifestations and severity of severe FXI deficiency varied and were not related to its activity. Three reported mutations and one novel frameshift mutation were identified, thus extending the mutation spectrum of FXI deficiency. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.