Factor XIII deficiency due to compound heterozygosity for 2 F13A1 variants

Background: Factor (F)XIII deficiency is a rare bleeding disorder. Genomic studies, adjunctive to biochemical assays, can provide valuable diagnostic and clinical clarity. Key Clinical Question: We describe a case of a child with FXIII deficiency in which genomic studies were crucial for accurate di...

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Bibliographic Details
Main Authors: Jodie Odame, Caroline Malcolmson, Cindy Wakefield, Tammy Bourque, David Lillicrap, Orla Rawley, Mackenzie Bowman, Manuel Carcao, Vanessa Bouskill
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037925003024
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Summary:Background: Factor (F)XIII deficiency is a rare bleeding disorder. Genomic studies, adjunctive to biochemical assays, can provide valuable diagnostic and clinical clarity. Key Clinical Question: We describe a case of a child with FXIII deficiency in which genomic studies were crucial for accurate diagnosis and treatment. Clinical Approach: An 8-year-old male presented with a severe bleeding phenotype. His FXIII antigen, activity, and alpha-subunit (FXIIIA) levels were below detection limits. Genetic analysis identified 2 likely pathogenic variants in F13A1: a novel nonsense variant (c.59_60del, p.Ser20X) and a missense variant (c.211G>A, p.Arg704Gln). Trio analysis revealed that compound heterozygosity for the p.Ser20X and p.Arg704Gln variants were causal for severe FXIIIA deficiency in the index case. Conclusion: Family segregation studies were essential in this case for interpreting genetic analysis results and identifying the causative variants resulting in severe FXIIIA deficiency.
ISSN:2475-0379