Analysis of clinical phenotype and genotype of two hereditary coagulation factor XII deficiency

Abstract

Objective Two Chinese pedigrees with congenital factor Ⅻ (FⅫ) deficiency were enrolled in the present study, and studies on the clinical manifestations, family survey, biochemical examinations and gene diagnosis of these pedigrees were performed. Methods In October 2014-2015 March, two cases of hereditary FⅫ deficiency patients were included in Xinhua hospital . Activated partial thromboplastin time(APTT), FⅫ procoagulant activity (FⅫ: C), FⅫ antigen(FⅫ: Ag)and other parameters of coagulant were detected. The FⅫ deficiency pedigree members, exons 1-14, boundary introns including the splice junctions of the F12 gene were amplified with polymerase chain reaction (PCR). Direct sequencing was exerted to purified PCR product to detect the gene mutation. If the gene mutations were found, polymorphism should be ruled out by directing sequence. One hundred and three healthy persons as normal controls. Results The two probands were manifested prolonged APTT (101 s and 143 s). They showed lower FⅫ activity and FⅫ antigen (2% and 6%, 0.4% and 4%, respectively). FⅡ: C, FⅦ: C, FⅧ: C, FⅨ: C, FⅩ: C and Fg are normal in the two probands. LAC is negative. Proband 1 has c. 1285C>T (p. Q429 stop) mutation. His parents and son have the heterozygous mutation in the same position. Proband 2 has c. 1556T>C(p.L519P)mutation. Her two sons have the heterozygous mutation in the same position. In the promoter regions of F12 gene, there were common 46C/T and 619 G/C polymorphisms in two pedigrees. Conclusion c. 1285C>T(p.Q429 stop)and c. 1556T>C(p.L519P)are the cause of FⅫ deficiency.(Chin J Lab Med, 2017, 40: 378-382) Key words: Factor Ⅻ deficiency; Factor Ⅻ; Mutation; Phenotype; Genotype; Pedigree