A novel homozygous mutation Leu519Arg in one pedigree with congenital factor XII deficiency

Abstract

To analyze the mutations of F12 genein one pedigree with congenital factor FXII (FXII) deficiency, and investigatethe molecular mechanisms of FXII deficiency. Methods Activated partial thromboplastin time(APTT), Prothrombin time(PT), FXII activity(FXII: C), FXII antigen(FXII: Ag) and other coagulant parameters were tested in the proband and his family members.5' and 3' UTR, all exons and their exon-intron boundaries of F12 gene were analyzed by direct sequencing.The detected mutations were confirmed by reverse sequencing. 100 healthy persons were as normal controls. Results The proband showed a markedly prolonged APTT (106.4s), the FXII: C and FXII: Ag were 2.0% and 1.0%, respectively. Hissecond daughter and granddaughter had slightly prolonged APTT, and other family members are normal. The FXII: C and FXII: Ag of family members were also decreased (his son, 23.0% and 21.0%; his elder daughter, 23.0% and 23.0%; his second daughter, 24.0% and 23.0%; hisgranddaughter, 23.0% and 23.0%). The phenotype of all members is consistent with cross-reactive material negative. Nucleotide sequencing analysis showed that the proband had missense mutations in the F12 gene, including one homozygous mutationc.1556T>G (p. Leu519Arg) and a commonly reported single nucleotide polymorphism site within the promoter region of the F12 gene (46T/T). Sequencing results from the proband' children demonstrate them as carriers of a heterozygous missense mutation. The proband's wife is normal and with 46C/C in the promoter region. Conclusion The c. 1556T>G in exon 13 is a novel mutation. This mutation affects FXIIcatalytic function, associated with a reduced level of FXII.(Chin J Lab Med, 2015, 38: 466-469) Key words: Factor Ⅻ deficiency; Pedigree; Homozygote; Mutation