Clinical features and molecular basis of 102 Chinese patients with congenital dysfibrinogenemia

• DOI: 10.1016/j.bcmd.2015.06.002
• Publication Date: 2015-06-14T17:03:46Z
• Authors: Jingyi Zhou; Qiulan Ding; Yaopeng Chen; Qi Ouyang; Linlin Jiang; Jing Dai; Yeling Lu; Xi Wu; Qian Liang; Hongli Wang; Xuefeng Wang
• Keywords: Adult; Male; 0301 basic medicine; China; Adolescent; Genotype; Fibrinogen; Middle Aged; Afibrinogenemia; Thrombelastography; 3. Good health; 03 medical and health sciences; Amino Acid Substitution; Asian People; Child, Preschool; Mutation; Humans; Female; Blood Coagulation Tests; Child; Blood Coagulation; Alleles; Aged

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).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.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.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.