Clinical and genetic analysis of 8 Chinese pedigrees with inherited dysfibrinogenemia / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To analyze clinical manifestation and genetic mutations in 8 Chinese pedigrees featuring hereditary dysfibrinogenemia.</p><p><b>METHODS</b>Prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), calibration of plasma protamine sulfate against TT, fibrinogen (Fg) activity, coagulation factors II, V, VII, VIII, IX, X, XI and XII of all probands and their family members were detected with an automatic blood coagulation analyzer; D-dimer(D-D) and fibrin(ogen) degradation products(FDPs) were also dtected by automatic blood coagulation analyzer, Fg antigen were detected with an immunoturbidimetry method. Exons of fibrinogen genes FGA, FGB and FGG and flanking sequences were amplified by polymerase chain reaction(PCR) and sequenced.</p><p><b>RESULTS</b>All of the probands showed normal levels of FDPs, D-dimer(D-D) and activity of coagulation factor II,V,VII, VIII, IX,X,XI, XII. Plasma PT and APTT were normal or slightly prolonged. Prolonged TT was found in all of the probands, whilst TT was not significantly shortened by protamine sulfate. Fg antigen was within the normal range, but Fg activity was significantly decreased. The Fg antigen/activity ratio was greater than 2. One proband has carried a heterozygous variant of the FGA gene g.1233G>A(p.A α Arg35His). Four have carried a heterozygous mutation of the FGB gene g.9692A>G(p.Bβ Asn190Ser). The remaining 3 had heterozygous substitution of FGG gene g.10819G>A(p.γ Arg301His). In addition, 2 polymorphisms (p.A α Thr331Ala) and p.B β Arg478Lys) were identified in FGA and FGB genes.</p><p><b>CONCLUSION</b>p.A α Arg35His, p.B β Asn190Ser and p. γ Arg301His are responsible for the inherited dysfibrinogenemia in the 8 Chinese pedigrees. p.B β Asn190Ser is firstly reported in China. p.B β Asn190Ser and p. γ Arg301His may be mutation hot spot in the Chinese population.</p>