Deutsch
Hrvatski
Русский
Português
GM2 Gangliosidosis Poodle Type
| Acronym: | GM2, Sandhoff disease |
| Gene: | HEXB |
| Mutation: | c.391delG |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
GM2 Gangliosidosis Poodle Type is a congenital lysosomal disorder affecting the Poodle dog breed and it is known as GM2 gangliosidosis variant 0. It is a progressive neurodegenerative disorder with a fatal outcome. GM2 belongs to a group of lysosomal disorders known as gangliosidosis, caused by the accumulation of lipids known as gangliosides. The gangliosidoses group of disorders, other than GM2, belongs to another disorder type, known as GM1. There are three variants of GM2 gangliosidosis, 0, B, and AB. Gangliosidosis variant 0 (GM2) has a human equivalent, known as Sandhoff disease, while in animals, GM2 has been identified in dogs, cats, pigs, deer, and flamingos.
GM2 gangliosidoses are a result of beta-hexosaminidase (Hex) deficiency, an enzyme that catalyzes the biodegradation of lipids gangliosides. This hydrolytic enzyme can be found in lysosomes. Hex is composed of two main isoenzymes, Hex A and Hex B, while only Hex A acts as the GM2 activator protein. Defects in the genes encoding for named proteins cause their improper function. In the case of the nonfunctioning beta-hexosaminidase enzyme, gangliosides start to accumulate, especially in the lysosomes of neurons, causing problems. Symptoms start to occur in the affected dog around 9 to 12 months of age. Neurological symptoms include a stiff gait, loss of balance, falling ataxia, intention tremor, postural deficit, astasia, decreased menace response, vision defect or loss, decreased corneal reflex, and decreased level of consciousness. In most of the affected dogs, another symptom was vomiting, without a known reason. A common finding in affected Toy Poodles was diffuse T2-hyperintensity of the subcortical white matter in the cerebrum, caused by hypoplasia of the myelin or delayed myelination, or both.
In general, clinical signs of GM2 Poodle Type are similar to those recognized previously in a Golden Retriever with GM2, with the same age of symptom onset. The main noticed difference between the GM2 Poodle type and Golden Retriever type was the loss of pupillary light reflexes, which was not recorded in Poodles. The GM2 is progressive, and the disorder usually ends fatal, with death onset between 18 to 23 months of age. GM2 Gangliosidosis Poodle Type is caused by deleterious mutations in the HEXB gene. HEXB gene is encoding β-subunit of lysosomal enzyme β –N-acetylhexosaminidase. GM2 is inherited as an autosomal recessive disorder. Healthy parents of an affected puppy are obligate heterozygotes and therefore carry one mutant allele. Heterozygotes have no symptoms. Dogs homozygous for the mutation will display the symptoms of the amelogenesis imperfecta. At conception, when mating two carrier dogs, each 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:
Rahman MM, Chang HS, Mizukami K, Hossain MA, Yabuki A, Tamura S, Kitagawa M, Mitani S, Higo T, Uddin MM, Uchida K, Yamato O. A frameshift mutation in the canine HEXB gene in toy poodles with GM2 gangliosidosis variant 0 (Sandhoff disease). Vet J. 2012 Dec;194(3):412-6.
Tamura S, Tamura Y, Uchida K, Nibe K, Nakaichi M, Hossain MA, Chang HS, Rahman MM, Yabuki A, Yamato O. GM2 gangliosidosis variant 0 (Sandhoff-like disease) in a family of toy poodles. J Vet Intern Med. 2010 Sep-Oct; 24(5):1013-9.