title: Genetic analysis in Factor XI deficient patients from central China: identification of one novel and seven recurrent mutations.
abstract: Factor XI (FXI) deficiency is a rare bleeding disorder with a range of manifestations from asymptomatic to trauma related bleeding. To identify mutations in FXI-deficient patients and characterize the phenotype-genotype relationship, we studied six patients and their 18 family members in central China. Five patients were identified by presurgical or routine laboratory screening but had no bleeding symptoms. Only one patient exhibited excessive injury- and surgical-related bleeding. Eight mutations were detected, including five nonsense mutations (p.Tyr369*, p.Arg72*, p.Gln281*, p.Trp519*, and p.Trp246*), two missense mutations (p.Thr40Ile and p.Ala430Thr), and a 4-bp deletion in a splice site (c.1136-4delGTTG); one mutation was novel (p.Thr40Ile). In vitro, the p.Thr40Ile mutant protein exhibited impaired secretion and function. Five of the patients were homozygous or compound heterozygous, but only one nonsense mutation was found in Patient 2. In these patients, bleeding tendency was not correlated with FXI levels or with a single heterozygous mutation. Thrombin generation tests could not distinguish the bleeder from non-bleeders. In conclusion, we reported 8 mutations in the FXI gene (F11) leading to FXI deficiency. Moreover, the functional consequences of a novel mutation leading to FXI deficiency have been elucidated. More cases are needed to find any signature of founder effect in the Chinese population and its potential relationship with other Asian population.
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Hui
authors: H
authors: Liu
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Hua-Fang
authors: HF
authors: Wang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China. Electronic address: lancet.tang@qq.com.
authors: Liang
authors: L
authors: Tang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Yan
authors: Y
authors: Yang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Qing-Yun
authors: QY
authors: Wang
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Wei
authors: W
authors: Zeng
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Ying-Ying
authors: YY
authors: Wu
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Zhi-Peng
authors: ZP
authors: Cheng
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Bei
authors: B
authors: Hu
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China.
authors: Tao
authors: T
authors: Guo
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, China. Electronic address: dr_huyu@126.com.
authors: Yu
authors: Y
authors: Hu
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002681:China; D004252:DNA Mutational Analysis; D005172:Factor XI / Q000235:genetics*; D005173:Factor XI Deficiency / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013917:Thrombin / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D005172:Factor XI; D013917:Thrombin
keywords: Factor XI deficiency; Hemorrhage; Mutation; Thrombin generation tests