Analysis of a Chinese pedigree affected with hereditary factor VII deficiency caused by compound heterozygous variants of F7 gene.
10.3760/cma.j.issn.1003-9406.2020.06.009
- Author:
Meina LIU
1
;
Yanhui JIN
;
Lihong YANG
;
Haixiao XIE
;
Xiaolong LI
;
Siqi LIU
;
Shasha LUO
;
Mingshan WANG
Author Information
1. Center of Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China. wywms@126.com.
- Publication Type:Journal Article
- From:
Chinese Journal of Medical Genetics
2020;37(6):633-636
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the molecular basis for a Chinese pedigree affected with hereditary coagulation factor VII (FVII) deficiency.
METHODS:The coding regions of F7 gene were amplified by PCR and sequenced. Suspected variants were confirmed by reverse sequencing and validated in other members from the pedigree. Pathogenicity of the variants was analyzed with multiple bioinformatic tools.
RESULTS:Genetic analysis revealed that the proband has carried compound heterozygous c.985T>C (p.Ser329Pro) and c.1091G>A (p.Arg364Gln) variants in exon 8 of the F7 gene. Her mother, brother and son were heterozygous for c.985T>C (p.Ser329Pro), while her father was heterozygous for c.1091G>A (p.Arg364Gln). Phylogenetic analysis suggested that both p.Ser329 and p.Arg364 are highly conserved among homologous species. Online bioinformatic software predicted both variants to be deleterious. Protein model analysis suggested that the Pro329 side chain may form a new hydrogen bond with Leu333. The Pro benzene ring may clash with Glu325 in the p.Ser329Pro variant model. The p.Arg364Gln variant have two additional hydrogen bonds compared with wild type Arg364. Both variants may lead to alteration of the protein structure.
CONCLUSION:The p.Ser329Pro and p.Arg364Gln variants in exon 8 of the F7 gene probably account for the reduced FVII in this pedigree.
