Testing of dogs: Cerebellar hypoplasia
Lissencephaly and cerebellar hypoplasia in White Swiss Shepherd Dogs
Cerebellar hypoplasia means incomplete development of the cerebellum. In White Swiss Shepherds, it occurs together with lissencephaly, a developmental defect characterised by an abnormal structure of the brain tissue, without the typical folds, co-called gyri and sulci on the cerebral cortex of the brain. The condition also accompanies moderate hydrocephalus with dilatation of the cerebral ventricles.
The disease manifests itself in puppies as early as 2 weeks of age with ataxia (impaired coordination of movement). Although the sucking reflex is fully developed, the puppies have difficulty in latching onto the breast, which is why they do not gain weight well. The gait is unsteady, wobbly, and coordination problems are also evident when standing. Clinical signs are progressive and lead to the need for euthanasia.
The disease is caused by mutation c. 2839del in the RELN gene, which encodes reelin, a secreted extracellular matrix glycoprotein involved in several steps of neuronal migration.
The mode of inheritance of the mutation is probably 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:
Littlejohn, M.D., Sneddon, N., Dittmer, K., Keehan, M., Stephen, M., Drögemüller, M., Garrick, D. : A frameshift-deletion mutation in Reelin causes cerebellar hypoplasia in White Swiss Shepherd dogs. Anim Genet , 2023. Pubmed reference: 37334487.