Unique de-novo mutation of fibrinogen gene in a Chinese girl with hypofibrinogenemia

Abstract

Hypofibrinogenemia is characterized by low plasma fibrinogen concentrations (<1.5 g/l). It is usually caused by heterozygous mutations in one of the three fibrinogen genes. To the best of our knowledge, the vast majority of these mutations have been proven to be inherited from a parent. We studied here a Chinese family in which the proband had low functional and antigen fibrinogen levels, 0.77 and 0.90 g/l, respectively. DNA sequencing revealed a novel Asp316His mutation in the γD domain of fibrinogen. However, both parents were negative for the mutation. Modeling analysis indicated that the Asp316His mutation may destabilize the conformation of the γ314-γ318 loop and lead to hypofibrinogenemia. Haplotype analysis of single-nucleotide polymorphisms excluded the possibility of nonpaternity, indicating it is a de-novo event. Further investigation of her living environment suggested the Asp316His mutation might have been induced by exposure to chromate mutagens.