Phenotype and genotype analysis of coagulation factor Ⅺ deficiency caused by a compound heterozygous mutation

doi:10.3969/j.issn.1673-8640.2020.10.016

Abstract

Abstract:

Objective To analyze the phenotype and genotype of a family with congenital coagulation factor（F） Ⅺ deficiency,and to investigate its molecular pathogenesis. Methods Peripheral blood samples of proband and family members（8 persons in 3 generations） were collected,and coagulation-related indicators in upper plasma were determined. Totally,13 exons and 5' non-translation regions of F11 were amplified by polymerase chain reaction（PCR）,and sequencing analysis was performed. The corresponding mutation sites of family members were detected. The segment with mutation was sequenced backward. The effects of mutation sites on proteins were analyzed by bioinformatics softwares（PolyPhen-2,Mutation Taster and SIFT）. Results The activated partial thromboplastin time（APTT） of proband was 162 s,FⅪ activity was 2%,and FⅪ antigen was 3.6%. His father,mother,sister and son all presented prolonged APTT with markedly decreased values of FⅪ activity and FⅪ antigen. Sequencing analysis showed cDNA.1640G>A and cDNA.2183G>A compound heterozygous mutations in F11 gene were from his father and mother,respectively. The results of bioinformatics softwares showed that the mutations could affect the function of protein and lead to the occurrence of corresponding diseases. Conclusions The compound heterozygous mutations of cDNA.1640G>A and cDNA.2183G>A in F11 gene may cause the decreased FⅪ activity in the patient.

Key words: Coagulation factor Ⅺ deficiency, Phenotype, Genotype, Molecular mechanism

CLC Number:

R446.1

BI Xiaojie, HUANG Daochao, JIN Xianfu, JIANG Junyu, SU Zhengxian, CHEN Chaochao, SHEN Bo. Phenotype and genotype analysis of coagulation factor Ⅺ deficiency caused by a compound heterozygous mutation[J]. Laboratory Medicine, 2020, 35(10): 1036-1039.

Figures/Tables 5

References 14

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家系成员	PT/s	APTT/s	FⅪ:C/%	FⅪ:Ag/%	TT/s	DD/（mg/L）	FDP/（mg/L）
先证者（Ⅱ3）	14.0	162	2	3.6	16.7	1.34	1.23
父亲（Ⅰ1）	14.2	86.5	25	25	17.2	0.23	0.34
母亲（Ⅰ2）	13.3	78.6	31	31	16.9	0.43	0.34
妻子（Ⅱ4）	13.8	40.2	98	100	15.8	0.26	0.34
儿子（Ⅲ2）	14.0	76.6	39	35	17.2	0.24	0.34
姐姐（Ⅱ2）	3.8	78.9	40	37	17.0	0.85	0.34
姐夫（Ⅱ1）	13.3	40.2	99	99	15.6	0.23	0.23
外甥女（Ⅲ1）	13.2	41.7	102	102	15.8	0.43	2.36
家系成员	FⅡ:C/%	FⅤ:C/%	FⅦ:C/%	FⅩ:C/%	FⅧ:C/%	FⅨ:C/%	FⅫ:C/%
先证者（Ⅱ3）	100	89	87	88	102	89	89
父亲（Ⅰ1）	99	95	99	89	95	95	103
母亲（Ⅰ2）	89	89	102	95	104	90	99
妻子（Ⅱ4）	95	95	89	105	88	90	95
儿子（Ⅲ2）	90	98	95	90	100	101	104
姐姐（Ⅱ2）	88	100	90	95	98	105	95
姐夫（Ⅱ1）	97	102	88	90	90	89	89
外甥女（Ⅲ1）	98	89	102	102	95	89	95

家系成员	PT/s	APTT/s	FⅪ:C/%	FⅪ:Ag/%	TT/s	DD/（mg/L）	FDP/（mg/L）
先证者（Ⅱ3）	14.0	162	2	3.6	16.7	1.34	1.23
父亲（Ⅰ1）	14.2	86.5	25	25	17.2	0.23	0.34
母亲（Ⅰ2）	13.3	78.6	31	31	16.9	0.43	0.34
妻子（Ⅱ4）	13.8	40.2	98	100	15.8	0.26	0.34
儿子（Ⅲ2）	14.0	76.6	39	35	17.2	0.24	0.34
姐姐（Ⅱ2）	3.8	78.9	40	37	17.0	0.85	0.34
姐夫（Ⅱ1）	13.3	40.2	99	99	15.6	0.23	0.23
外甥女（Ⅲ1）	13.2	41.7	102	102	15.8	0.43	2.36
家系成员	FⅡ:C/%	FⅤ:C/%	FⅦ:C/%	FⅩ:C/%	FⅧ:C/%	FⅨ:C/%	FⅫ:C/%
先证者（Ⅱ3）	100	89	87	88	102	89	89
父亲（Ⅰ1）	99	95	99	89	95	95	103
母亲（Ⅰ2）	89	89	102	95	104	90	99
妻子（Ⅱ4）	95	95	89	105	88	90	95
儿子（Ⅲ2）	90	98	95	90	100	101	104
姐姐（Ⅱ2）	88	100	90	95	98	105	95
姐夫（Ⅱ1）	97	102	88	90	90	89	89
外甥女（Ⅲ1）	98	89	102	102	95	89	95

家系成员	突变基因		基因型
家系成员	Ala430Thr	Val611Met	基因型
先证者（Ⅱ3）	+	+	复合杂合型
父亲（Ⅰ1）	+	-	杂合型
母亲（Ⅰ2）	-	+	杂合型
妻子（Ⅱ4）	-	-	-
儿子（Ⅲ2）	-	-	-
姐姐（Ⅱ2）	-	+	杂合型
姐夫（Ⅱ1）	-	-	-
外甥女（Ⅲ1）	-	-	-

家系成员	突变基因		基因型
家系成员	Ala430Thr	Val611Met	基因型
先证者（Ⅱ3）	+	+	复合杂合型
父亲（Ⅰ1）	+	-	杂合型
母亲（Ⅰ2）	-	+	杂合型
妻子（Ⅱ4）	-	-	-
儿子（Ⅲ2）	-	-	-
姐姐（Ⅱ2）	-	+	杂合型
姐夫（Ⅱ1）	-	-	-
外甥女（Ⅲ1）	-	-	-

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