Jiang S. · Chen Y. · Liu M. · Zeng M. · Yang L. · Jin Y. · Jia K. · Wang M.

Author affiliations

Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Article / Publication Details

Received: November 14, 2021
Accepted: December 05, 2022
Published online: December 21, 2022

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 3

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA

Abstract

Introduction: Mutations in the F11 gene can cause factor XI (FXI) deficiency, leading to abnormal coagulation activity and injury-related bleeding tendency. Therefore, identifying F11 gene mutations and studying the molecular basis will help us understand the pathogenesis of FXI deficiency. Methods: Coagulation tests and gene sequencing analysis of all members were performed. FXI wild-type and mutant expression plasmids were constructed and transfected into HEK293FT cells. The FXI protein expression level was evaluated by ELISA and Western blot. Results: The FXI activity (FXI:C) and FXI antigen (FXI:Ag) of proband-1 were decreased to 2% and 5%, respectively. FXI:C and FXI:Ag of proband-2 were reduced to 15% and 32%, respectively. Four mutations were found in the two unrelated families, including c.536C>T (p.T179M), c.1556G>A (p.W519*), c.434A>G (p.H145R), and c.1325_1325delT (p.L442Cfs*8). In vitro studies in transiently transfected HEK293FT cells demonstrated that p.T179M, p.W519*, and p.L442Cfs*8 mutations significantly lowered the FXI levels in the culture media. The FXI levels in the culture media and cell lysates of p.H145R mutation were similar to the wild type. Conclusion: Our results confirm that the four mutations in the F11 gene are causative in the 2 FXI deficiency families. Moreover, the p.H145R mutation is a cross-reactive material (CRM)-positive phenotype. The other three mutations are CRM-negative phenotypes and lead to FXI protein secretion disorder.

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Received: November 14, 2021
Accepted: December 05, 2022
Published online: December 21, 2022

Number of Print Pages: 11
Number of Figures: 6
Number of Tables: 3

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: https://www.karger.com/AHA

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