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Warburg Micro Syndrome 1 (WARBM1) – Alaskan Husky
| Acronym: | WARBM1 |
| Gene: | RAB3GAP1 |
| Mutation: | c.614_615insN[218] |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Warburg Micro Syndrome 1 (WARBM1) is an inherited neurological disorder affecting Alaskan huskies, also known as polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV). The disorder is part of a wider group of disorders, commonly known as polyneuropathies, which are characterized by damage to peripheral nerves. The same named disorder affects human patients in which clinical signs include microphthalmia, microcornea, bilateral congenital cataracts, short palpebral fissures, optic atrophy, mental retardation, etc. The phenotype of affected Alaskan Huskier resembles a similar disorder in Rottweilers, known as neuronal vacuolation and spinocerebellar degeneration, and also in Boxers and Black Russian Terriers, known as polyneuropathy with ocular abnormalities and neuronal vacuolation.
On examined affected dogs the neurological signs started around 4-5 months of age with visual problems, accompanied by changes in the voice 1-2 months later. Around 6-10 months of age, the dog displayed severe spinal ataxia, with more severely affected pelvic limbs where postural reactions were completely absent. Ophthalmologic examination showed bilateral microphthalmia, small pupils, and lenses with nuclear cataracts. Strabismus and/or persistent pupillary membranes may be present. MRI findings showed thinning of the white matter of the forebrain and corpus callosum. In superficial dorsolateral white matter, lesions may be prominent, and areas of axonal and myelin loss are replaced by gliotic tissue. In the spinal cord gray matter subtle to severe neuronal vacuolation is present. In the Purkinje cells, severe loss and degeneration are observed. Due to the severity of the symptoms, dogs are usually euthanized between 8 to 16 months of age.
Warburg Micro Syndrome 1 in Alaskan husky is caused by a mutation in the RAB3GAP1 gene. RAB3GAP1 protein is part of a protein complex crucial for intracellular vesicle trafficking. The disorder is inherited in an autosomal recessive pattern. A dog can be clear, carrier, or affected. Carriers of the gene are heterozygous and do not develop the disease’s symptoms. When mating two carrier dogs, each future cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
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. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not 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.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Wiedmer, M., Oevermann, A., Borer-Germann, S. E., Gorgas, D., Shelton, G. D., Drögemüller, M., … Leeb, T. (2016). A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities, and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1). G3: Genes|Genomes|Genetics, 6(2), 255–262. http://doi.org/10.1534/g3.115.022707