Background: Mutations in the F10-coding gene can cause factor X (FX) deficiency, leading to abnormal coagulation activity and severe tendency for hemorrhage. Therefore, identifying mutations in F10 is important for diagnosing congenital FX deficiency. Methods: We studied a 63-year-old male patient with FX deficiency and 10 of his family members. Clotting and immunological methods were used to determine activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen levels, FX activity, and FX antigen levels. The platelet count was determined. A mixing study was performed to eliminate the presence of coagulation factor inhibitors and lupus anticoagulant. Mutations were searched using whole-exome sequencing and certified by Sanger sequencing. Results: Genetic analysis of the proband identified two single-base substitutions: c.1085G>A (p.Ser362Asn) and c.1152C>A (p.Tyr384Ter, termination codon, caused by the DNA sequence TAA). His FX activity and antigen levels were 1.7% and 408.53 pg/mL, respectively; aPTT and PT were 52.3 and 48.0 s, respectively. One brother had the same compound heterozygous mutations, and his FX activity and antigen levels were 1.3% and 465.47 pg/mL, respectively; his aPTT and PT were 65.2 and 54.5 s, respectively. His mother, another brother, and one sister were heterozygous for c.1085G>A (p.Ser362Asn), and his daughter and grandson (6 years old) were heterozygous for c.1152C>A (p.Tyr384Ter). Conclusion: The heterozygous variants p.Ser362Asn or p.Tyr384Ter indicate mild FX deficiency, but the compound heterozygous mutation of the two causes severe congenital FX deficiency and bleeding. Genetic analysis of these two mutations may help characterize the bleeding tendency and confirm congenital FX deficiency.

1.
Borhany
M
,
Buthiau
D
,
Rousseau
F
,
Guillot
O
,
Naveena
F
,
Abid
M
, et al
Genotyping of five Pakistani patients with severe inherited factor X deficiency: identification of two novel mutations
.
Blood Coagul Fibrinolysis
.
2018
Nov
;
29
(
7
):
622
5
.
[PubMed]
0957-5235
2.
Al Dieri
R
,
Peyvandi
F
,
Santagostino
E
,
Giansily
M
,
Mannucci
PM
,
Schved
JF
, et al
The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding
.
Thromb Haemost
.
2002
Oct
;
88
(
4
):
576
82
.
[PubMed]
0340-6245
3.
Sivapalaratnam
S
,
Collins
J
,
Gomez
K
.
Diagnosis of inherited bleeding disorders in the genomic era
.
Br J Haematol
.
2017
Nov
;
179
(
3
):
363
76
.
[PubMed]
0007-1048
4.
Uprichard
J
,
Perry
DJ
.
Factor X deficiency
.
Blood Rev
.
2002
Jun
;
16
(
2
):
97
110
.
[PubMed]
0268-960X
5.
Kanade
GD
,
Pingale
KD
,
Karpe
YA
.
Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E Virus and Are Possibly Implicated in ORF1 Polyprotein Processing
.
J Virol
.
2018
Feb
;
92
(
6
):
e01853
17
.
[PubMed]
0022-538X
6.
Dewerchin
M
,
Liang
Z
,
Moons
L
,
Carmeliet
P
,
Castellino
FJ
,
Collen
D
, et al
Blood Coagulation Factor X Deficiency Causes Partial Embryonic Lethality and Fatal Neonatal Bleeding in Mice
.
J Thromb Haemost
.
2000
;
83
(
2
):
185
90
. 1538-7933
7.
Tai
SJ
,
Herzog
RW
,
Margaritis
P
,
Arruda
VR
,
Chu
K
,
Golden
JA
, et al
A viable mouse model of factor X deficiency provides evidence for maternal transfer of factor X
.
J Thromb Haemost
.
2008
Feb
;
6
(
2
):
339
45
.
[PubMed]
1538-7933
8.
Togashi
T
,
Nagaya
S
,
Nagasawa
M
,
Meguro-Horike
M
,
Nogami
K
,
Imai
Y
.
Genetic analysis of a compound heterozygous patient with congenital factor X deficiency and regular replacement therapy with a prothrombin complex concentrate
.
Int J Hematol
.
2019
Oct
;
•••
: ; [
Epub ahead of print
].
[PubMed]
0925-5710
9.
Mezzano
D
,
Quiroga
T
.
Diagnostic challenges of inherited mild bleeding disorders: a bait for poorly explored clinical and basic research
.
J Thromb Haemost
.
2019
Feb
;
17
(
2
):
257
70
.
[PubMed]
1538-7933
10.
van Dievoet
MA
,
Jacquemin
M
,
Van Calsteren
K
,
Peerlinck
K
.
A rare presentation of homozygous factor X deficiency in a pregnant patient: A case report and review of the literature
.
Haemophilia
.
2019
Jan
;
25
(
1
):
e57
9
.
[PubMed]
1351-8216
11.
Girolami
A
,
Scandellari
R
,
Scapin
M
,
Vettore
S
.
Congenital bleeding disorders of the vitamin K-dependent clotting factors
.
Vitam Horm
.
2008
;
78
:
281
374
.
[PubMed]
0083-6729
12.
Menegatti
M
,
Peyvandi
F
.
Factor X deficiency
.
Semin Thromb Hemost
.
2009
Jun
;
35
(
4
):
407
15
.
[PubMed]
0094-6176
13.
Mannucci
PM
,
Duga
S
,
Peyvandi
F
.
Recessively inherited coagulation disorders
.
Blood
.
2004
Sep
;
104
(
5
):
1243
52
.
[PubMed]
0006-4971
14.
Girolami
A
,
Cosi
E
,
Santarossa
C
,
Ferrari
S
,
Girolami
B
,
Lombardi
AM
.
Factor X Friuli Coagulation Disorder: Almost 50 Years Later
.
Clin Appl Thromb Hemost
.
2018
Jan
;
24
(
1
):
33
40
.
[PubMed]
1076-0296
15.
Wang
WB
,
Fu
QH
,
Zhou
RF
,
Wu
WM
,
Ding
QL
,
Hu
YQ
, et al
Molecular characterization of two novel mutations causing factor X deficiency in a Chinese pedigree
.
Haemophilia
.
2005
Jan
;
11
(
1
):
31
7
.
[PubMed]
1351-8216
16.
Ding
Q
,
Shen
Y
,
Yang
L
,
Wang
X
,
Rezaie
AR
.
The missense Thr211Pro mutation in the factor X activation peptide of a bleeding patient causes molecular defect in the clotting cascade
.
Thromb Haemost
.
2013
Jul
;
110
(
1
):
53
61
.
[PubMed]
2567-689X
17.
Lu
Q
,
Yang
L
,
Manithody
C
,
Wang
X
,
Rezaie
AR
.
Molecular basis of the clotting defect in a bleeding patient missing the Asp-185 codon in the factor X gene
.
Thromb Res
.
2014
Nov
;
134
(
5
):
1103
9
.
[PubMed]
0049-3848
18.
Jin
Y
,
Cheng
X
,
Zheng
J
,
Xia
H
,
Yang
L
,
Wang
M
.
A novel factor X mutation Cys81 by Arg and a reported factor VII polymorphism Arg353 replaced by Gln co-occured in a patient
.
Blood Coagul Fibrinolysis
.
2018
Jan
;
29
(
1
):
67
74
.
[PubMed]
0957-5235
19.
Simeoni
I
,
Stephens
JC
,
Hu
F
,
Deevi
SV
,
Megy
K
,
Bariana
TK
, et al
A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders
.
Blood
.
2016
Jun
;
127
(
23
):
2791
803
.
[PubMed]
0006-4971
20.
Richards
S
,
Aziz
N
,
Bale
S
,
Bick
D
,
Das
S
,
Gastier-Foster
J
, et al;
ACMG Laboratory Quality Assurance Committee
.
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology
.
Genet Med
.
2015
May
;
17
(
5
):
405
24
.
[PubMed]
1098-3600
21.
Menegatti
M
,
Peyvandi
F
.
Treatment of rare factor deficiencies other than hemophilia
.
Blood
.
2019
Jan
;
133
(
5
):
415
24
.
[PubMed]
0006-4971
22.
Ersayin
A
,
Thomas
A
,
Seyve
L
,
Thielens
N
,
Castellan
M
,
Marlu
R
, et al
Catalytically inactive Gla-domainless factor Xa binds to TFPI and restores ex vivo coagulation in hemophilia plasma
.
Haematologica
.
2017
Dec
;
102
(
12
):
e483
5
.
[PubMed]
0390-6078
23.
Muller
MP
,
Wang
Y
,
Morrissey
JH
,
Tajkhorshid
E
.
Lipid specificity of the membrane binding domain of coagulation factor X
.
J Thromb Haemost
.
2017
Oct
;
15
(
10
):
2005
16
.
[PubMed]
1538-7933
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