MUTATION REPORTTwo heterozygous mutations associated with type I protein C deficiency in two Chinese independent familiesXu, Qiyu; Wang, Mingshan; Jin, Yanhui; Liu, Siqi; Luo, Shasha; Yang, LihongAuthor Information Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China Correspondence to Lihong Yang, Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, Ouhai District, Wenzhou 325000, China Tel: +86 57788069594; fax: +86 57788069596; e-mail: [email protected] Received 1 March, 2021 Revised 23 June, 2021 Accepted 5 July, 2021 Blood Coagulation & Fibrinolysis: December 2021 - Volume 32 - Issue 8 - p 596-602 doi: 10.1097/MBC.0000000000001065 Buy Metrics Abstract To explore the pathogenesis of protein C (PC) deficiency in two independent families by mutations detection and bioinformatics analysis. The PC activity (PC:A) and PC antigen (PC:Ag) were detected by chromogenic substrate and ELISA, respectively. The PROC sequencing was performed to identify the mutational sites. The molecular pathogenesis of the mutations were studied by the conservation, bioinformatics and model analysis. The PC:A and PC:Ag of the proband 1 were observably reduced at 35 and 44%, respectively. Gene sequencing analysis revealed the p.Leu278Pro derived from a heterozygous c.833T>C point mutations in exon 9 of PROC gene. For proband 2, the PC:A and PC:Ag were decreased to 40 and 51%, respectively, caused p.Ala178Pro missense mutation by a heterozygous point mismatch of c.532G>C in exon 5 of PROC gene. Bioinformatics and model analysis indicated that it was the Leu278Pro and Ala178Pro that caused clinical PC deficiency (PCD). The heterozygous mutations Leu278Pro and Ala178Pro were observed in two independent families. The Leu278Pro mutation in the PROC gene has not been described elsewhere. The two mutations can both lead to the type I hereditary PCD, and probably be the major causes of PCD in the families. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.