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Severe Combined Immunodeficiency Frisian Water Dog Type (SCID)
| Acronym: | SCID |
| Gene: | RAG1 |
| Mutation: | c.2893G>T |
| Inheritance: | Autosomal recessive |
| Sample type: | Cheek Swab, Whole Blood (EDTA) |
Genetics and characteristics
Severe Combined Immunodeficiency Frisian Water Dog Type Type (SCID) is a lethal genetic immunodeficiency disorder affecting the Frisian Water Dog breed. Generally, severe combined immunodeficiency refers to a group of genetic disorders, which are characterized by T- and B- lymphocyte dysfunction, which causes an impaired immune system and death at a young age. SCID affects humans, mice, horses, and dogs. In humans, SCID is colloquially known as ”bubble boy” disease, since the patients require complete clinical isolation in aim to avoid any contact with environmental microbes and infections. Among dogs, except in Frisian Water Dogs, it has been diagnosed among Jack Russell Terriers, Basset Hounds, and Cardigan Welsh Corgies, but each is caused by a distinct causative mutation. The disorder has a different inheritance pattern depending on the breed, in Jack Russel Terriers and Frisian Water Dogs SCID is inherited in an autosomal recessive pattern and the X-linked form of SCID has been identified in Basset Hounds and Cardigan Welsh Corgies.
Unexplained pup mortality has been observed to occur in approximately 10% of all Frisian Water Dog litters. The clinical signs included diarrhea, the development of epileptic seizures, and vestibular ataxia. Pathological features included multifocal chronic encephalitis, multifocal pyogranulomatous lesions in various organs, and depletion of lymphoid tissues, which suggests immunodeficiency as a cause of death. Differential white blood cell counts by blood smear show decreased numbers of lymphocytes. Observed percentages were less than 1%, while normal rage is between 16-51%. There have not been detected immunoglobulin M (IgM) levels. Since IgM is not one of the maternal antibodies obtained from mother to puppy, its absence indicates an inborn deficiency. The IgA and IgG levels were not detectable, or very low.
Severe Combined Immunodeficiency Frisian Water Dog Type is caused by a mutation in the RAG1 gene. The frameshift mutation causes premature stop codon and production of a truncated protein, disrupting the catalytic activity of RAG1 involved in the V(D)J recombination and antibody production. The causative mutation of SCID in Jack Russell Terriers has not been detected in affected Frisian Water Dogs, making these two mutations distinct and specific for the breed. SCID Frisian Water Dog Type is inherited in an autosomal recessive pattern. Healthy parents of the 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 SCID. 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:
Verfuurden, B., Wempe, F., Reinink, P., van Kooten, P. J. S., Martens, E., Gerritsen, R., Vos, J. H., Rutten, V. P. M. G, Leegwater, P. A. (2011) Severe combined immunodeficiency in Frisian Water Dogs caused by a RAG1 mutation. Genes and Immunity 12, 310–313; doi:10.1038/gene.2011.6.