Genetic Mutation Linked to Developmental Epileptic Encephalopathy in Bengal Kitten

An important discovery in veterinary genetics has emerged from the case of a Bengal kitten diagnosed with a mutation causing developmental and epileptic encephalopathy type 50 (DEE50), a severe neurometabolic disorder in humans. This condition stems from mutations in the CAD gene, essential for producing pyrimidine nucleotides—crucial components in DNA and RNA. The discovery, published in *Scientific Reports* on June 24, 2025, underscores the significance of cross-species genetic research and highlights the potential of animal models to advance understanding of rare diseases.

The Bengal kitten, which began exhibiting seizures at 13 weeks of age, experienced symptoms including body stiffness, facial twitching, and drooling. Initial veterinary assessments, which included blood tests and MRI scans, failed to identify a clear cause. Despite treatment with antiepileptic medications, the kitten's condition deteriorated, leading its owners to opt for humane euthanasia. Post-euthanasia investigations uncovered a rare mutation in the CAD gene (XP_011279586.1:p.Ser2015Asn), which disrupts the gene's function responsible for nucleotide synthesis.

Dr. Ava Landry, a PharmD candidate at the University of Connecticut and lead author of the study, noted that this mutation significantly impairs the CAD protein's structure and activity. "The findings indicate that this genetic variant leads to profound metabolic consequences, mirroring symptoms observed in human cases of DEE50," Dr. Landry stated.

To validate the impact of the mutation, researchers used a human CAD-knockout cell line, which requires uridine for growth. The introduction of wild-type CAD allowed these cells to thrive in uridine-free environments, while cells with the Ser2015Asn mutation failed to grow, confirming the mutation's detrimental effect.

In a broader context, the study included genetic screening of 110 Bengal cats, revealing that while four healthy cats carried one copy of the mutation, none had two copies, suggesting a recessive inheritance pattern. This indicates the mutation’s prevalence is low within the breed but warrants further genetic screening in Bengal cats to prevent the reproduction of affected kittens.

The case represents the first documented instance of CAD deficiency in felines, providing an invaluable model for studying DEE50. The research emphasizes the need for effective treatments in both veterinary and human medicine. Although the Bengal kitten did not receive uridine therapy, previous human studies suggest that this supplement could reverse seizures and improve developmental outcomes by utilizing a bypass pathway in nucleotide synthesis.

The implications of this discovery extend beyond veterinary applications. The findings may lead to new strategies for diagnosing and treating DEE50 in humans, offering hope for improved interventions. Dr. Sarah Johnson, a neuroscientist at Stanford University, commented, "This study illustrates the potential for animal models to illuminate the pathways of human diseases, ultimately paving the way for innovative treatment approaches."

In conclusion, the identification of a CAD mutation in a Bengal kitten not only sheds light on a rare genetic disorder but also reinforces the importance of interdisciplinary research in advancing medical science. The continued exploration of such genetic parallels promises to enhance both veterinary and human healthcare, providing new avenues for understanding and treating complex conditions like DEE50.