Clinical Genetics
Analysis of PROC gene variant in a Chinese pedigree affected with hereditary protein C deficiency
Chen Yuan, Shi Jiamin, Huang Xiaoxia, Sheng Anqun, Lu Chaosheng, Zhu Mianmian, Wang Qiu, Wan Mingshang, Wang Dan
Published 2022-11-10
Cite as Chin J Med Genet, 2022, 39(11): 1233-1237. DOI: 10.3760/cma.j.cn511374-20210809-00661
Abstract
ObjectiveTo explore the molecular pathogenesis of a Chinese pedigree affected with inherited protein C (PC) deficiency.
MethodsThe 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.
ResultsThe 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).
ConclusionThe 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.
Key words:
Hereditary protein C deficiency; PROC gene; Genetic variant
Contributor Information
Chen Yuan
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Shi Jiamin
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Huang Xiaoxia
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Sheng Anqun
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Lu Chaosheng
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Zhu Mianmian
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Wang Qiu
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Wan Mingshang
Department of Medical Laboratory Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
Wang Dan
Department of Pediatrics, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
