Factor XIII deficiency in two Spanish families with a novel variant in gene F13A1 detected by next-generation sequencing
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Factor XIII deficiency in two Spanish families with a novel variant in gene F13A1 detected by next‑generation sequencing; symptoms and clinical management Andrés Moret1 · Ángel Zúñiga2 · Javier Marco Ayala1 · Alessandro Liquori2 · Ana Rosa Cid1 · Saturnino Haya1 · Fernando Ferrando1 · Amando Blanquer1 · José Cervera2 · Santiago Bonanad1
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Coagulation factor XIII (FXIII) has a major role in coagulation stabilizing the haemostatic clot. FXIII deficiency is associated with an increased risk of bleeding. Severe phenotypes lead to spontaneous, traumatic and surgical bleeding. Umbilical cord bleeding is especially common, and intracranial bleeding may occur in up to one third of patients without prophylaxis. In this work, we used NGS for screening all the coding and intronic boundary regions of F13A1 and F13B genes in two families affected by severe FXIII deficiency. Outcome confirmation analysis and variant studies in related patients was done by Sanger sequencing. Two variants were found: c.34A > G (p.Arg12Gly; NM_00129.3) and c.514C > T (p.Arg172Ter; NM_00129.3), both located in the F13A1 gene. The variant p.Arg172Ter is already described in literature and was found in homozygosis in one family and in compound heterozygosis in the other family. The variant p.Arg12Gly variant has not been described previously. This variant is located in the activation peptide of the FXIII A-subunit which is highly conserved among FXIII homologs. Given the high risk of dangerous bleeding and early manifestation in severe FXIII-deficient patients, a prompt genetic confirmation is imperative. In this sense, NGS technology allows a rapid and simultaneous analysis of all regions of all the genes involved in the pathology. Keywords Bleeding · FXIII deficiency · Genetics · High-throughput sequencing
Highlights • Severe Factor XIII deficiency can lead to dangerous
bleeding early in life.
• Factor XIII deficiency in two families has been character-
ized and genotyped.
• A new mutation in F13A1 gene has been described. • NGS is a useful tool for studying inherited bleeding
coagulation disorders.
* Ángel Zúñiga [email protected] 1
Unidad de Hemostasia Y Trombosis, Servicio de Hematología, Hospital Universitario Y Politécnico La Fe, Valencia, Spain
Unidad de Genética, Servicio de Hematología, Hospital Universitario Y Politécnico La Fe, Avinguda de Fernando Abril Martorell, 106, 46026 Valencia, Spain
2
Introduction Coagulation factor XIII (FXIII) has a major role in coagulation. Activated FXIII catalyses the formation of covalent bonds between fibrin polymers, stabilizing the haemostatic clot. Besides improving the integrity of the clot, FXIII is able to crosslink to the clot other plasma proteins such as fibronectin, α2-antiplasmin or thrombin activable fibrinolysis inhibitor, that will play further roles in the haemostatic process. Congenital FXIII deficiency is a rare bleeding disorder, with a prevalence estimated at 1 in 2 million people [1]. FXIII
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