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Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes
Published on: June 3, 2014
Factor XIII deficiency due to compound heterozygosity for 2 F13A1 variants
Jodie Odame1, Caroline Malcolmson1, Cindy Wakefield1,2
1Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Faculty of Medicine, Toronto, Canada.
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.
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