A novel homozygous missense mutation (Met527Ile) in a consanguineous marriage family with inherited factor XII deficiency

Abstract

Objective: To identify potential mutations of the FXII gene (F12) in a consanguineous marriage family with hereditary coagulation factor XII (FXII) deficiency, and it will improve the understanding of the pathogenesis involved in the disease. Clinical presentation: The proband was a 58-year-old male who had chronic gastritis. He was found to have a significantly prolonged activated partial thromboplastin time (APTT) at 101.0s (reference range, 29.0-43.0 s) before stomachendoscopy. Techniques: The coagulation factor XII activity (FXII:C) and FXII antigen (FXII:Ag) were measured by one-stage clotting assay and enzyme-linked immunosorbent assay, respectively. The F12 gene was amplified by polymerase chain reaction and sequenced. Mutation sites were further confirmed by reverse sequencing. The conservatism and possible impact of the amino acid substitution were analyzed by multiple bioinformatics tools, as well as 3D protein model analysis. Results: The proband had a prolonged APTT (101.0 s), whose FXII:C and FXII:Ag were obviously reduced, both at 1.0% (normal range, 72-113%). Gene sequencing revealed that he carried a homozygous missense mutation of Met527Ile. Family study showed that his mother, son and daughter carried a heterozygous Met527Ile. Bioinformatics and model analysis of the mutation indicated that Met527Ile may be detrimental and potentially alters the structure and the function of the protein. Conclusion:The novel mutation Met527Ile could potentially account for the reduced activity of FXII in this family.

A Novel Homozygous Missense Mutation (Ile583Asn) in a Consanguineous Marriage Family with Hereditary Factor XII Deficiency: A Case Report

“…10 Congenital FXII deficiency can be divided into two types: The cross-reacting material-negative group (CRM À ) is characterized by synchronously decreased FXII:C and FXII:Ag, whereas CRM-positive group (CRM þ ) has the feature of decreased activity but borderline-normal or normal antigen. 11 In this study, the FXII:C and FXII:Ag of the patient were significantly reduced simultaneously. Genetic analysis showed that the patient had a c.1748T > A homozygous missense mutation in exon 14 of the F12 gene, which led to the replacement of isoleucine (ATC) with asparagine (AAC) at amino acid position 583 (p.Ile583Asn).…”

Analysis of Hereditary FXII Deficiency Caused by Three Mutations Including a Novel Mutation

“…Patients exhibit prolonged activated partial thromboplastin time (aPTT) in vitro, but there is no significant predisposition to bleeding as expected. Most cases are typically identified incidentally during routine health checks or preoperative coagulation screening tests [ 1 , 2 ]. This report describes two Chinese patients with FXII deficiency, neither of whom had significant abnormal bleeding symptoms as expected.…”