Novel mutations (gamma Trp208Leu and gamma Lys232Thr) leading to congenital hypofibrinogenemia in two unrelated Chinese families

摘要

Congenital hypofibrinogenemia is a rare disorder caused by heterozygous mutations in the fibrinogen genes. The aim of this study was to elucidate the molecular defects in two unrelated families with hypofibrinogenemia. The proband from family A was a 19-year-old Chinese boy who was suffering from cervical lymphadenitis. A low plasma fibrinogen concentration (0.63 g/l by Clauss method and 0.77 g/l by immunoturbidimetry) was found in routine clotting tests. Further gene analysis revealed a heterozygous g. 5792 G>T mutation in exon 7 of the FGG, leading to a novel Trp208Leu change in the gamma D domain. This mutation was also found in other family members with low fibrinogen levels. The proposita from family B was a 37-year-old female who suffered from recurrent shoulder pain for 7 years. Routine clotting studies revealed that her prothrombin time was 15.5 s (normal range: 11.8-14.8 s) and thrombin time was 22.8 s (normal range: 14.0-20.0 s), and the fibrinogen concentration in her plasma was only 0.64 g/l by Clauss method and 0.79 g/l by immunoturbidimetry. A heterozygous A>C transition at nucleotide 5864 of FGG was found in the gamma chain, causing a Lys232Thr substitution in the fibrinogen. Further sequencing established that her mother, son, brother and nephew were also heterozygous for the mutation. Blood Coagul Fibrinolysis 25: 894-897 (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.