F13B – Factor XIII B-subunit Deficiency

The association between F13B and factor XIII, b subunit, deficiency of is supported by autosomal recessive inheritance in a single consanguineous pedigree presenting with severe bleeding. In the seminal report, a 32-year-old proband and her brother exhibited undetectable FXIII-B levels and markedly reduced FXIII activity due to a homozygous splice-site variant, c.65-2del, segregating with disease in heterozygous parents (PMID:2334637). No additional unrelated probands have been documented, and segregation analysis identifies one additional affected sibling, consistent with limited clinical validity (gene–disease association: Limited).

Functional studies confirm that FXIII-B stabilizes FXIII-A in plasma: absence of FXIII-B shortens the half-life of FXIII-A in vivo and in vitro disruption of structural disulfide bonds in FXIII-B impairs its secretion and stability (PMID:2334637; PMID:31013569). A rare homozygous founder mutation in a Japanese patient also led to alloantibody formation against FXIII-B upon replacement therapy, illustrating clinical challenges in management (PMID:23407795).

Key Take-home: Genetic testing for F13B variants together with FXIII antigen and activity assays enables definitive diagnosis and informs tailored prophylactic and replacement strategies.

References

• British journal of haematology | 1990 | A familial factor XIII subunit B deficiency. PMID:2334637
• Thrombosis and haemostasis | 2013 | Alloantibodies against the B subunit of plasma factor XIII developed in its congenital deficiency. PMID:23407795
• International journal of molecular sciences | 2019 | Disruption of Structural Disulfides of Coagulation FXIII-B Subunit; Functional Implications for a Rare Bleeding Disorder. PMID:31013569

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