A novel homozygous mutation Leu519Arg in one pedigree with congenital factor XII deficiency
10.3760/cma.j.issn.1009-9158.2015.07.011
- VernacularTitle:新的纯合子 Leu519 Arg 导致的遗传性凝血因子Ⅻ缺陷症家系分析
- Author:
Liya DAI
;
Deting ZHANG
;
Yingyu WANG
;
Yu TONG
;
Jun LI
;
Mingshan WANG
- Publication Type:Journal Article
- Keywords:
Factor Ⅻdeficiency;
Pedigree;
Homozygote;
Mutation
- From:
Chinese Journal of Laboratory Medicine
2015;(7):466-469
- CountryChina
- Language:Chinese
-
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 F 12 gene, including one homozygous mutationc.1556T >G ( p.Leu519Arg) and a commonly reported single nucleotide polymorphism site within the promoter region of the F 12 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 .
