Analysis of PROC gene variant in a Chinese pedigree affected with hereditary protein C deficiency.
10.3760/cma.j.cn511374-20210809-00661
- Author:
Yuan CHEN
1
;
Jiamin SHI
;
Xiaoxia HUANG
;
Anqun SHENG
;
Chaosheng LU
;
Mianmian ZHU
;
Qiu WANG
;
Mingshan WANG
;
Dan WANG
Author Information
1. Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. wd2014@126.com.
- Publication Type:Journal Article
- MeSH:
Humans;
China;
Mutation;
Pedigree;
Protein C/genetics*;
Protein C Deficiency/genetics*;
Male;
Female
- From:
Chinese Journal of Medical Genetics
2022;39(11):1233-1237
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the molecular pathogenesis of a Chinese pedigree affected with inherited protein C (PC) deficiency.
METHODS:The protein C activity (PC:A) and protein C antigen (PC:Ag) of the proband and his family members were determined by a chromogenic substrate method and enzyme-linked immunosorbent assay, respectively. The proband was subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing of other members of the pedigree.
RESULTS:The PC:A and PC:Ag of proband were reduced to 15% and 11%, respectively. The above parameters of his parents and elder sister were also decreased to approximately 50% of reference values. Next generation sequencing has revealed that the proband has harbored a heterozygous c.572_574delAGA (p.Glu191_Lys192delinsGlu) variant in exon 7 and a missense c.752C>T (p.Ala251Val) variant in exon 8 of the PROC gene. His father was heterozygous for the c.572_574delAGA variant, while his mother and elder sister were heterozygous for the c.752C>T variant. According to the American College of Medical Genetics and Genomics Standards and Guidelines, the c.572_574delAGA (p.Glu191_Lys192 delinsGlu) variant was predicted to be likely pathogenic (PS1+PM4+PP3). c.752 C>T (p.Ala251Val) variant was also likely pathogenic (PS1+PM1+PP3).
CONCLUSION:The deletional variant of c.572_574delAGA (p.Glu191_Lys192delinsGlu) in exon 7 and missense variant c.752C>T (p.Ala251Val) in exon 8 of the PROC gene probably underlay the inherited protein C (PC) deficiency in this pedigree. Above finding has enriched the spectrum of PROC gene variants and provided a basis for genetic counseling for this pedigree.
