Abstract: Background Congenital thrombocytopenia has not previously been reported in cats. We recently identified suspected congenital mild thrombocytopenia in Bengal cats that were either clinically asymptomatic or exhibited mild coagulation abnormalities. Hypothesis/Objectives To identify the genetic basis of suspected congenital thrombocytopenia in Bengal cats. Animals Thirty-two Bengal cats, including a family of six cats with one affected individual and an additional cohort of 26 unrelated cats. Methods Whole-genome sequencing was performed using peripheral blood DNA from the family to identify candidate genetic variants associated with thrombocytopenia. The identified variant was subsequently genotyped in all 32 cats using Sanger sequencing. Platelet count and size were assessed using automated hematology, flow cytometry and peripheral blood smear evaluation. Results Whole-genome sequencing identified a single candidate missense variant in GP1BA (c.32C>T) by comparison of the affected cat with five unaffected relatives. Genotyping revealed 3 homozygous, 7 heterozygous, and 22 wild-type cats. All homozygous cats had thrombocytopenia (85,000–160,000/µL on blood smears) at a young age (7 months–1 year at presentation), which was non-progressive, and were clinically asymptomatic or had mild coagulation abnormalities. These cats had macrothrombocytes, with mean platelet volumes exceeding 20 fL. One heterozygous cat showed mild thrombocytopenia, whereas the remaining heterozygous and all wild-type cats had platelet counts within reference intervals. Conclusions and clinical importance A GP1BA gene variant is strongly associated with congenital thrombocytopenia in Bengal cats. This condition should be considered in young Bengal cats presenting with persistent mild thrombocytopenia and large platelets.
