Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis

Yu, Yongjian1,2; Liu, Shengguo1,2; Han, Xuemei1,2; Xiao, Lu1,2,3; Huang, Qijun1,2; Li, Shulin1,2; Zhuang, Kaixue1,2; Yang, Mo3; Zou, Chang2,4; Fu, Yingyun1,2

2019-07-23

10.1111/jcmm.14563

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE   影响因子和分区

1582-1838

1582-4934

Pathogenic mutation of protein C (PROC) gene results into the deficiency of PROC activity. This study aimed to identify the pathogenic genetic variants and to explore the functional consequence in Chinese familial venous thrombosis (VTE). Whole exome sequencing was performed to identify the pathogenic variants of anticoagulant factors. Serum coagulation and anti-coagulation factors activity were assayed to evaluate the genetic association. Functional study of PROC antigen secretion deficiency was conducted in VTE subjects and in vitro cell lines. One rare pathogenic variant (p.Ala178Pro) was identified in the four VTE subjects but not in the normal subjects from the family. An inframeshift variant (rs199469469) was also identified in a paediatric subject of the pedigree. Further evaluation of serum PROC activity levels in p.Ala178Pro variants VTE carriers showed significantly lower PROC activity compared to non-carriers. Furthermore, in vitro study showed that the p.Ala178Pro mutant cells had a consistent reduction in concentration of PROC antigen. In conclusions, our study demonstrated the pathogenic variant (p.Ala178Pro) contributed to PROC type I activity deficiency, which may be due to decreased secretion of PROC.

p Ala178Pro PROC deficiency rs199469469 venous thromboembolism whole exome sequencing

SCI

英语

第一 ; 通讯

National Key Research and Development Program of China[2016YFC1304400]

Cell Biology ; Research & Experimental Medicine

Cell Biology ; Medicine, Research & Experimental

WOS:000484202300001

WILEY

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Southern Univ Sci & Technol, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Inst Shenzhen Resp Dis,Key Lab Shenzhen Resp Dis, Shenzhen, Guangdong, Peoples R China
2.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen, Guangdong, Peoples R China
3.Sun Yat Sen Univ, Affiliated Hosp 7, Shenzhen, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Clin Med Res Ctr, Shenzhen, Guangdong, Peoples R China

Yu, Yongjian,Liu, Shengguo,Han, Xuemei,et al. Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2019,23(10):7099-7104.

Yu, Yongjian.,Liu, Shengguo.,Han, Xuemei.,Xiao, Lu.,Huang, Qijun.,...&Fu, Yingyun.(2019).Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,23(10),7099-7104.

Yu, Yongjian,et al."Pathogenic variants of PROC gene caused type I activity deficiency in a familial Chinese venous thrombosis".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 23.10(2019):7099-7104.