Phenotype and genotype diagnosis of 6 pedigrees with inherited coagulation factor Ⅹ deficiency

doi:10.16150/j.1671-2870.2020.01.006

Abstract

Abstract:

Objective: To investigate the molecular pathogenesis of 6 pedigrees with inherited coagulation factorⅩ (FⅩ) deficiency and to assess the bleeding risk in patients with inherited FⅩ deficiency by thrombin generation test (TGT).Methods: Clinical data of the 6 pedigrees were collected. The FⅩ coagulation activity (FⅩ:C) was tested by clotting test and FⅩ antigen (FⅩ:Ag) was detected by double antibody sandwich enzyme-linked immunosorbent assay（ELISA）. The concentration of FⅩ in plasma was measured with Western blotting. The FⅩ gene (F10) mutation was analyzed by direct sequencing. Thrombin generation (TG) in six patients and some family members was measured using TET. Results: Ten F10 mutations were identified in 6 probands, five of which (p.Cys 246 Ser, p.Tyr 319 Cys, p.Leu 252 Phe, p.Arg 313 Gln and p. IVS5-2A>G) were novel and the other five(p.Phe71Ser, p.Val 338 Met, p.Gly 406 Ser, p.Gly 365 Ser and p.Cys 151 Arg) had been previously reported. TGT showed that endogenous thrombin potential (ETP) and peak height (Peak) had certain correlation with bleeding severity of FX-deficient patients. Conclusions: Five noval mutations of FⅩ are identified. Five patients were resulted from compound heterozygous F10 mutations, while the remaining one is caused by one heterozygous F10 mutation. TGT parameters including ETP and Peak could be used to assess the bleeding risk in patients with FⅩ deficiency, and TGT might serve as a useful laboratory tool to monitor the risk of bleeding.

Key words: Coagulation factor Ⅹ deficiency, Thrombin generation test, Phenotype, Genotype

CLC Number:

R446

LIU Jiajie, SHAO Yanyan, LIANG Qian, DING Qiulan. Phenotype and genotype diagnosis of 6 pedigrees with inherited coagulation factor Ⅹ deficiency[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(1): 20-27.

Figures/Tables 7

References 20

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先证者	性别/ 年龄（岁）	临床表现	出血评分(分)	APTT (s)	PT (s)	FⅩ∶C			FⅩ∶ Ag	分型	基因检测
先证者	性别/ 年龄（岁）	临床表现	出血评分(分)	APTT (s)	PT (s)	APTT途径	PT途径	RVV途径	FⅩ∶ Ag	分型	基因检测
1	男/10	皮肤淤斑,换牙时出血, 肌肉出血	7	74.1	28.9	2.4	2.6	2.4	7.3	Ⅰ型	c.212T>C, p.Phe71Ser; c.1012G>A,p.Val338Met
2	女/79	月经量多,手术后出血难止,拔牙后出血	4	42.7	15.8	38.9	42.2	44.4	83.1	Ⅱ型	c.1216G>A, p.Gly406Ser
3	女/36	月经量多,外伤后出血难止	6	48.3	20.2	15.8	16.8	12.3	67.6	Ⅱ型	c.736T>A, p.Cys246Ser; c.956A>G, p.Tyr319Cys
4	女/24	自发鼻出血,皮肤易发淤斑,牙龈出血	4	55.9	26.5	4.2	7.2	6.2	35.4	Ⅱ型	c.1093G>A, p.Gly365Arg; c.754C>T, p.Leu252Phe
5	男/13	无出血症状	0	38.8	16.3	27.9	12.7	16.7	18.2	Ⅰ型	c.938G>A, p.Arg313Gln; IVS5-2A>G
6	男/26	鼻出血,牙龈出血,皮肤易发淤斑,关节出血,肌肉血肿	10	52.5	30.6	3.8	2.4	2.5	5.6	Ⅰ型	c.212T>C, p.Phe71Ser; c.451T>C, p.Cys151Arg

患者及家系成员	LT(min)	ETP (nmol*min)	峰值(nmol)	TTP(min)
P1-(Ⅱ-1)	13.33	98.23	3.77	28.67
P1-(Ⅰ-1)	7.00	408.12	41.61	12.67
P1-(Ⅰ-2)	6.76	626.77	33.18	17.12
P2-(Ⅱ-1)	7.83	763.50	55.81	15.17
P3-(Ⅱ-1)	10.33	224.32	15.60	17.67
P3-(Ⅲ-1)	9.00	944.50	88.70	14.67
P4-(Ⅱ-1)	30.32	99.90	5.04	40.84
P5-(Ⅱ-1)	7.83	295.56	26.57	13.83
P5-(Ⅰ-1)	6.00	764.93	68.50	12.00
P6-(Ⅱ-1)	5.17	83.91	3.04	14.67
正常对照者	6.17	969.31	92.49	11.67