title: Clinical features and molecular basis of 102 Chinese patients with congenital dysfibrinogenemia.
abstract: BACKGROUND
  Congenital dysfibrinogenemia (CD) is a rare qualitative disorder of fibrinogen (Fg) with heterogeneous clinical manifestations. We aimed to analyze clinical phenotype and molecular basis of 102 Chinese CD patients and to evaluate the application of thromboelastography (TEG).
  
  
  METHODS
  Clinical manifestations were recorded and quantified using the consensus ISTH bleeding assessment tool. Kaolin activated TEG and functional Fg TEG were applied in 30 patients. Genetic analysis of Fg genes were performed by direct sequencing.
  
  
  RESULTS
  27.5% patients experienced bleeding, 3.9% had thrombosis and 68.6% were asymptomatic. Females were more prone to experience bleeding (P=0.01). Significant difference (P<0.05) in TEG results were found between patients with hot-spot mutations at AαArg35(16) and γArg301(275), but were not identified between patients with and without bleeding. Normal TEG results were found in patients with mutations at AαArg35(16), AαPro37(18) or AαArg38(19). Six novel mutations were identified, including AαGly33(14)del, AαAsp57(38)_Trp60(41)delIVS2+1_+2GTdel, AαPhe742(723)Tyr, γAsn334(308)Thr, γGly335(309)Cys and γTrp395(369)Leu.
  
  
  CONCLUSIONS
  CD patients have similar clinical manifestations and hot-spot mutations worldwide with no ethnic difference. TEG results could not indicate the bleeding risk in patients, but priority of mutation screening at thrombin cleavage site or polymerization site on Aа chain may be given if TEG results are normal.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Qiulan
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Laboratory Medicine, The 303 Hospital of Chinese People's Liberation Army, China.
authors.forename: Yaopeng
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Yeling
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China. Electronic address: wangxuefeng6336@hotmail.com.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013916:Thrombelastography; D055815:Young Adult
chemical_list: D005340:Fibrinogen
keywords: Congenital; Dysfibrinogenemia; Hemorrhage; Mutation; Thromboelastography