Coonhound puppy with severe bleeding linked to F13A1 gene defect

Abstract

BACKGROUND: Factor XIII (FXIII) deficiency is a rare autosomal recessive bleeding disorder characterized by unstable fibrin clots and severe hemorrhagic complications. In humans, pathogenic variants have been described in F13A1 and F13B, which encode the subunits comprising the FXIII heterotetramer. However, cases in animals are exceedingly rare. HYPOTHESIS/OBJECTIVES: The objective of this work was to characterize a naturally occurring FXIII deficiency in a dog. ANIMALS: A 4-month-old male Black and Tan Coonhound presented with spontaneous hemoperitoneum, thrombocytopenia, and persistent bleeding after surgical procedures. METHODS: Hemostasis testing and whole genome sequencing were performed to characterize the phenotypic and molecular genetic basis of the bleeding disorder. RESULTS: A functional FXIII deficiency was identified, and a private, homozygous variant (c.1234_1239delinsTCAA) was found in exon 11 of F13A1 that predicts a frameshift and premature stop codon. CONCLUSIONS AND CLINICAL IMPORTANCE: This report represents only the second clinical description of FXIII deficiency in dogs and the first genetic characterization of this disorder in companion animals. The identified F13A1 variant provides a molecular diagnosis and enables genetic testing for this bleeding disorder in Black and Tan Coonhounds should additional cases arise.