A novel fibrinogen variant: dysfibrinogenemia associated with γAsp185Asn substitution.

To identify the pathogenesis of a Chinese woman diagnosed with dysfibrinogenemia. A patient from Nanjing presented with a low plasma concentration of fibrinogen and a normal level of antigen of fibrinogen. This abnormality was also detected in her son. To detect whether the genetic mutation was responsible for the dysfibrinogenemia, genomic DNA was extracted and amplified by polymerase chain reaction, and DNA sequencing was performed on the purified PCR products. Restriction fragment length polymorphism (RFLP), molecular modeling and homologous sequences alignment were performed. Two heterozygous missense variants, AαArg16His and γAsp185Asn, were discovered in the proband. Only the former was detected in her son. AαArg16His had been reported by other teams, and γAsp185Asn was identified first in our study as a novel variant. RFLP was performed and indicated that the novel failed to be found in normal subjects. Furthermore, it was suggested to be responsible for dysfibrinogenemia depending on the molecular modeling and homologous sequence alignment. The heterozygous AαArg16His and γAsp185Asn identified in the study probably underlie the dysfibrinogenemia in this pedigree, with the latter being identified for the first time.