Mitochondrial fission encephalopathy (MFE) in Bull Mastiffs

Mitochondrial encephalopathy is a brain disease characterized by many neurological abnormalities. It involves moderate to severe hydrocephalus with dilatation of all ventricles and the cerebral aqueduct. The cerebellar nuclei have an altered colour and structure that is spongy with gliosis. Mitochondria are multiplied and often abnormally shaped.

Clinical signs begin to appear at 6 months of age. These are progressive gait and behavioural abnormalities. The most prominent findings are ataxia (impaired coordination of movements), visual impairment and behavioural changes.

The disease is caused by mutation c.471_475delinsCGCTCT in the MFF gene, which encodes a mitochondrial fission factor.

The mode of inheritance of the mutation is autosomal recessive. This means that only individuals who inherit the mutated gene from both parents will develop the disease. Carriers of the mutated gene are clinically healthy but pass the mutation on to their offspring. In the case of a mating between two heterozygous individuals, theoretically 25% of the offspring will be completely healthy, 50% of the offspring will be carriers and 25% of the offspring will inherit the mutated gene from both parents and will therefore be affected by the disease.

The genetic test can clearly reveal the genotype of the animal and is a useful tool for breeders to prevent unintentional breeding of affected puppies.

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References:

Christen, M., Gutierrez-Quintana, R., Vandenberghe, H., Kaczmarska, A., Penderis, J., José-López, R., Rupp, A., Griffiths, I.R., Jagannathan, V., Leeb, T. : Mitochondrial fission factor (MFF) frameshift variant in Bullmastiffs with mitochondrial fission encephalopathy. Anim Genet 53:814-820, 2022. Pubmed reference: 36085405