Clinical manifestations and gene analysis of 18 cases of hereditary protein S deficiency.
10.3760/cma.j.issn.0253-2727.2022.01.010
- VernacularTitle:遗传性蛋白S缺乏症18例临床表现与基因分析
- Author:
Dong Lei ZHANG
1
;
Feng XUE
1
;
Rong Feng FU
1
;
Yun Fei CHEN
1
;
Xiao Fan LIU
1
;
Wei LIU
1
;
Yu Jiao JIA
1
;
Hui Yuan LI
1
;
Yu Hua WANG
1
;
Zhi Jian XIAO
1
;
Lei ZHANG
1
;
R C YANG
1
Author Information
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
- Publication Type:Journal Article
- Keywords:
High throughput sequencing;
PROS1 gene;
Protein S;
Thromboembolism
- MeSH:
Antithrombin III/genetics*;
Female;
Genetic Testing;
Humans;
Mutation;
Pregnancy;
Protein C/genetics*;
Protein S/genetics*;
Protein S Deficiency/genetics*
- From:
Chinese Journal of Hematology
2022;43(1):48-53
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To analyze the clinical manifestations and molecular pathogenesis of 18 patients with inherited protein S (PS) deficiency. Methods: Eighteen patients with inherited PS deficiency who were admitted to the Institute of Hematology & Blood Diseases Hospital from June 2016 to February 2019 were analyzed: activity of protein C (PC) and antithrombin (AT) , PS activity were measured for phenotype diagnosis; high throughput sequencing (HTS) was used for screening of coagulation disease-related genes; Sanger sequencing was used to confirm candidate variants; Swiss-model was used for three-dimensional structure analysis. Results: The PS:C of 18 patients ranged from 12.5 to 48.2 U/dL. Among them, 16 cases developed deep vein thrombosis, including 2 cases each with mesenteric vein thrombosis and cerebral infarction, and 1 case each with pulmonary embolism and deep vein thrombosis during pregnancy. A total of 16 PROS1 gene mutations were detected, and 5 nonsense mutations (c.134_162del/p.Leu45*, c.847G>T/p.Glu283*, c.995_996delAT/p.Tyr332*, c.1359G> A/p.Trp453*, c.1474C>T/p.Gln492*) , 2 frameshift mutations (c.1460delG/p.Gla487Valfs*9 and c.1747_1750delAATC/p.Asn583Wfs*9) and 1 large fragment deletion (exon9 deletion) were reported for the first time. In addition, the PS:C of the deep vein thrombosis during pregnancy case was 55.2 U/dL carrying PROC gene c.565C>T/p.Arg189Trp mutation. Conclusion: The newly discovered gene mutations enriched the PROS1 gene mutation spectrum which associated with inherited PS deficiency.
