Genetic analysis for a haemophilia B family with multi nucleotides deletion mutation of F9 gene

Objective To conduct genetic diagnosis and prenatal diagnosis for a haemophilia B family with multi-nucleotides deletion mutation of F9 gene. Methods This is a genetic analysis. Whole exon mutation of the F9 gene was analyzed by PCR and Sanger sequencing for seven patients with the family of hemophilia B who consulted doctors in Henan Province People′s Hospital in April 2013. Suspected mutation was verified among non-hemophilia B members of the family and 100 healthy controls to rule out genetic polymorphism of the F9 gene. The above-mentioned detection results of hemophilia B gene, the pathogenic mutation of F9 gene in the family was clarified, and prenatal diagnosis was conducted for the female carriers in the family.It is recommended that the fetal gene detection should be conducted in amniotic fluid in the mid-term pregnancy of the female carriers of hemophilia, and then they can be informed of the non-hemophilia B fetus by the results of the gene detection. Results PCR and sequencing analysis has identified a deletion mutation of F9 gene c. 185_188delGAGA[p.Glu62Asnfs*41]in seven hemophilia B patients. This mutation induced F9 gene frame shift mutation which led to early termination of F9 gene translation because there was a termination codon TAA at the 41th codon after the mutation site. The same mutation was not found among the non-hemophilia B members of the family and the 100 healthy controls. There were eight female carriers and nine female non-carriers in the family. Upon prenatal diagnosis, the Y chromosome sex-determining gene (SRY) in amniotic fluid was positive and no deletion mutation was observed in the F9 gene c. 185_188. Conclusion The pathogenic mutation of F9 gene in the family was identified, which was helpful for prenatal diagnosis in female carriers.(Chin J Lab Med, 2018, 41: 675-679) Key words: Hemophilia B; Gene deletion; Prenatal diagnosis; Genetic testing