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Alexander disease Labrador Retriever Type
| Acronym: | AxD |
| Gene: | GFAP |
| Mutation: | c.719G>A |
| Inheritance: | Autosomal dominant |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Alexander disease Labrador retriever type is a rare neurodegenerative disorder characterized by astrocyte dysfunction. The disorder is also known as Leukodystrophy in Labrador retrievers. Alexander disease is generally not common in dogs, but it has been recognized in several species. It has been diagnosed in humans, dogs, and sheep. Among dogs, AxD has been reported in Labrador retrievers, Bernese mountain dogs, Scottish Terriers, miniature poodles, and Chihuahua. The causative mutation has been identified in the Labrador retriever breed. Alexander disease can be divided into three types (infantile, juvenile, and adult), dependent on the age of onset and the clinical signs. Another classification system can be based on clinical signs, by which we recognize type I and type II AxD. Alexander disease in Labrador retrievers can be compared with the juvenile type of the disorder in men, based on symptoms and age of their onset.
Astrocytes are a type of glial cells in the brain and spinal cord. One of the main compounds of astrocytes is the glial fibrillary acidic protein (GFAP). Astrocytic protein aggregates are a pathological feature termed Rosenthal fibers. These fibers mainly contain GFAP and are a result of a mutation within the GFAP coding gene, which is specific for Alexander disease. Affected Labrador retrievers start to show symptoms by 4 to 6 weeks of age. Symptoms include severe tetraplegia, spastic forelimbs, and mild vestibular signs. Histopathological examination reveals numerous intra-astrocytic Rosenthal fibers in the brain and spinal cord with large GFAP accumulation. Due to the severity of the neurological symptoms, affected puppies usually need to be euthanized.
Leukodystrophy Labrador retriever type or Alexander disease is caused by a mutation in the GFAP gene. The mutation causes a G to A nucleotide substitution which results in an Arginine to Histidine amino acid substitution. The disorder is inherited in an autosomal dominant pattern. This means that one copy of the mutated gene is enough for a dog to develop the symptoms of the disorder.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Van Poucke, M., Martlé, V., Van Brantegem, L., Ducatelle, R., Van Ham, L., Bhatti, S., & Peelman, L. J. (2016). A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. European Journal of Human Genetics, 24(6), 852–856. http://doi.org/10.1038/ejhg.2015.223