Haemophilia A in a Female German Shepherd With Homozygosity for the FVIII p. C567Y Variant in Exon 11 of the

ABSTRACT

Haemophilia A is an extremely rare disorder in females, as the causative F8 gene is located on the X chromosome. Female carriers, also known as ‘conductors,’ are typically heterozygous and therefore do not show clinical signs of the disease. However, in mild forms of haemophilia A, affected males may survive and mate. In such cases, mating a haemophilic male with a carrier female can result in female offspring who are homozygous for a pathogenic variant and consequently develop haemophilia A. In the present case, a female dog with a mild form of haemophilia A is described. Although it had a markedly increased bleeding tendency, bleeding episodes have so far not been fatal. There were no prior indications of haemophilia A inheritance in either parent. To identify a causative variant in the F8 gene, whole‐genome sequencing was performed on the affected dog. A homozygous missense variant was identified in exon 11 of the F8 gene, resulting in an amino acid substitution within the A2 domain of factor VIII—a region critical for the stability and function of the coagulation factor. The same variant has previously been described in an unrelated German Shepherd. Notably, many examined variants along the entire X chromosome of the dog were homozygous. The rediscovery of this variant, more than 10 years after its initial description, underscores the importance of comprehensive genetic diagnostics, especially in rare diseases with atypical inheritance patterns.