[Homozygous missense mutation p.Val298Met of F10 gene causing hereditary coagulation factor X deficiency in a Chinese pedigree].
OBJECTIVE
To identify potential mutation underlying coagulation factor X (FX) deficiency in a consanguineous Chinese pedigree.


METHODS
Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FX activity (FX:C) and other coagulant parameters were determined with a one-stage clotting assay. The FX antigen (FX:Ag) was determined with an ELISA assay. All coding exons and exon-intron boundaries of the F10 gene were amplified with PCR and subjected to direct sequencing. Suspected mutation was confirmed by reverse sequencing and analyzed with CLC Genomics Workbench 7.5 software.


RESULTS
The PT and APTT in the proband were prolonged to 67.2 s and 102.9 s, respectively. Further study showed that her FX:C and FX:Ag were reduced by 1% and 8%, respectively. The PT of her father, mother, and little brother were slightly prolonged to 14.5 s, 14.4 s and 14.4 s, respectively. The FX:C and FX:Ag in her father, mother and little brother were all slightly reduced. Genetic analysis of the proband has revealed a homozygous G>A change at nucleotide 27881 in exon 8 of the F10 gene, which predicted a p.Val298Met substitution. The proband's father, mother, and little brother were all heterozygous for the p.Val298Met mutation. The proband has inherited the homozygous mutation from her parents by consanguineous marriage. Other family members were all normal. Bioinformatics analysis has indicated that this mutation may result in changes in the secondary structure of the FX protein.


CONCLUSIONS
A homozygous mutation g.27881G>A(p.Val298Met) of the F10 gene has been identified, which probably accounts for the low FX concentrations in this pedigree.
Laboratory Medicine Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China. wywms@126.com.
Yanhui
Y
Jin
Xiuping
X
Hao
Xiaoli
X
Cheng
Lihong
L
Yang
Yi
Y
Chen
Haixiao
H
Xie
Yingyu
Y
Wang
Mingshan
M
Wang
D000328:Adult; D000595:Amino Acid Sequence; D003241:Consanguinity; D005170:Factor X / Q000235:genetics*; D005171:Factor X Deficiency / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011517:Prothrombin Time
D005170:Factor X