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GM1 Gangliosidosis Portuguese Water Dog Type
| Acronym: | GM1 |
| Gene: | GLB1 |
| Mutation: | c.179G>A |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
| Method: | Sanger sequencing |
Genetics and characteristics
GM1 Gangliosidosis Portuguese Water Dog Type is a congenital lysosomal disorder affecting the Portuguese Water Dog breed. It is a progressive neurodegenerative disorder with a fatal outcome. GM1 belongs to a group of lysosomal disorders known as gangliosidosis, caused by the accumulation of lipids gangliosides. The gangliosidoses group of disorders, other than GM1, belongs to another disorder type, known as GM2. There are three forms of GM1: early infantile, late infantile, and adult. Except in Portuguese Water Dogs, GM1 has been reported in Friesian cattle, Siamese and Korat cats, English springer spaniels, and mixed breed beagle dogs. Beta-galactosidase is a hydrolase enzyme located in the lysosomes. It catalyzes the breakage of a glycosidic bond, resulting in the hydrolysis of beta-galactosides into monosaccharides. When the gene encoding for the beta-galactosidase enzyme is deficient, abnormal storage of acidic lipid materials in cells of the central and peripheral nervous system occurs. GM1 is characterized by the low or absent activity of this enzyme in the brain and liver.
The first symptoms occur between 5 to 6 months of age. The incorrect function of the cerebellum in affected dogs results in progressive neurological degradation and asymmetric growth. Dogs show loss of coordination, muscle tremors, muscle ataxia, loss of weight, and wide-based gait. The disorder may have an impact on the dog’s eyes as well, due to lesions of the retina and clouding of the cornea. Degenerative eye changes will be first seen as squinting and in end will progress to complete blindness. Behavioral changes will be present as well. Microscopic examination reveals occasionally swollen axons and demyelinated fibers in white matter. These findings were most numerous in the cerebellum, corpus callosum, internal capsule in the brain, and all white matter tracts of the spinal cord. Examination of the ultrastructure of swollen axons shows increased numbers of intact and degenerating mitochondria, membrane-bound dense or vacuolated bodies, and occasional inclusions. Due to the severity and progressive nature of the disorder, dogs are usually euthanized due to humane reasons or die by the age of 1 year.
GM1 Gangliosidosis Portuguese Water Dog Type is caused by deleterious mutations in the GLB1 gene encoding for lysosomal enzyme β -galactosidase. GM1 is inherited as an autosomal recessive disorder. The dog can be clear, carrier, or affected. 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 GM1. 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:
Saunders GK, Wood PA, Myers RK, Shell LG, Carithers R. GM1 gangliosidosis in Portuguese water dogs: pathologic and biochemical findings. Vet Pathol. 1988 Jul;25(4):265-9.
Wang ZH, Zeng B, Shibuya H, Johnson GS, Alroy J, Pastores GM, Raghavan S, Kolodny EH. Isolation and characterization of the normal canine beta-galactosidase gene and its mutation in a dog model of GM1-gangliosidosis. J Inherit Metab Dis. 23 (2000) 593-606.