Clinical and genotypic analysis of two Chinese pedigrees affected with hereditary coagulable factor VII deficiency.
10.3760/cma.j.issn.1003-9406.2019.03.007
- Author:
Fanfan LI
1
;
Jie LIU
;
Qianying ZHU
;
Chenfang SHEN
;
Kuangyi SHU
;
Xiao YANG
;
Wei YANG
;
Suzhen LIN
;
Bi CHEN
;
Minghua JIANG
Author Information
1. Department of Laboratory Medicine, the Second Affiliated Hospital, Wenzhou Medical University , Wenzhou, Zhejiang 325027, China. minghua93@126.com.
- Publication Type:Journal Article
- MeSH:
Asian Continental Ancestry Group;
Factor VII;
Factor VII Deficiency;
Genotype;
Heterozygote;
Humans;
Mutation;
Pedigree
- From:
Chinese Journal of Medical Genetics
2019;36(3):221-224
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor VII(FVII) deficiency.
METHODS:The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species.
RESULTS:For proband of pedigree 1, the prothrombin time (PT), FVII activity (FVII:C) and FVII antigen (FVII:Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c.80_81delCT and c.1371G>T(p.Arg439Ser). His son carried a heterozygous c.1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FVII:C and FVII:Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c.278G>T(p.Arg75Met) missense variant in exon 3 and c.1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c.278G>T(p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p.Arg439Ser and p.Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids.
CONCLUSION:Two novel heterozygous missense variants of the F7 gene [c.1371G>T(p.Arg439Ser) and c.278G>T(p.Arg75Met)] probably account for the decrease of factor VII in the two pedigrees.
