Severe Combined Immunodeficiency Frisian Water Dog Type (SCID)
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 in 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 patter and the X-linked form of SCID has been identified in Basset Hounds and Cardigan Welsh Corgies.
Characteristics and Symptomes
An unaxplained pup mortality has been observed to occur in approximately 10% of all Frisian Water Dog litters. The clinical signs included diarrhea, development of epileptic seizures and vestibular ataxia. Pathological features included multifocal chronic encephalitis, multifocal pyrogranulomatous 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 has not been detected any 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 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 mutation distinct and specific for the breed.
SCID Frisian Water Dog Type is inherited in an autosomal recessive pattern. Healthy parents of 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.
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.