A novel Cys328-terminator mutant implicated in severe coagulation factor XIII deficiency: a case report
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CASE REPORT
Open Access
A novel Cys328-terminator mutant implicated in severe coagulation factor XIII deficiency: a case report Ruimin Cai, Yi Li, Wenyang Wang and Qiang Feng*
Abstract Background: Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder that is commonly due to mutations in the FXIIIA subunit gene (F13A1), and it has been reported to have a prevalence of one per 2 million. We describe a new genetic variant in the F13A1 gene that caused a patient to suffer from lifelong hemorrhagic diathesis. Case presentation: We evaluated a 20-year-old female with umbilical cord bleeding after birth, an intracerebral hemorrhage at age 6, and other bleeding episodes, including hematuria and cephalohematoma, who suffered from a lifelong hemorrhagic diathesis. The clot solubility test showed that the clot of the patient was dissolved in urea solution at 10 h. Genetic testing identified a novel homozygous mutation, c.984C > A(p. Cys328stop), resulting in a premature stop codon in exon 8 of the F13A1 gene. The results obtained with ClusterX software showed that Cys328 of exon 8 in the F13A1 gene is highly conserved among species. Conclusion: We reported a novel homozygous mutation in the F13A1 gene in a factor XIII (FXIII)-deficient patient, which adds a new point mutation to the mutant library. In this paper, we discuss other aspects of the disease, including laboratory examination, homogeneous sequence alignment and molecular modeling. Keywords: Bleeding disorder, Factor XIII deficiency, Point mutation, A-subunit
Background Coagulation factor XIII (FXIII) is a plasma transglutaminase that is activated in the clotting cascade, which is essential for the final step in the blood coagulation process [1]. Plasma FXIII (pFXIII) is a tetramer composed of two A-subunits and two B-subunits. The A-subunits have catalytic function, and the B-subunits do not have enzymatic activity and may serve as plasma carrier molecules [2]. After cleavage of the peptide by thrombin in the presence of calcium ions, pFXIII dissociates from its B-subunits and yields the active enzyme factor XIIIa. This enzyme acts as a transglutaminase to catalyze the
* Correspondence: [email protected] Department of Clinical Laboratory, Taian City Central Hospital, No. 29, Longtan Road, Taishan District, Taian 271000, Shandong Province, China
formation of γ-glutamyl-ε-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot [3]. pFXIII A-subunits are expressed mainly in the placenta, urinary bladder, gall bladder and bone marrow; the pFXIII A-subunit gene consists of 15 exons, and the B-subunit gene is composed of 12 exons, while its expression is restricted to the liver. FXIII deficiency is classified into two categories: type I deficiency, which is characterized by the lack of both the A and B subunits; and type II deficiency, which is characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion and can even cause crippling
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