Mucopolysaccharidosis VI in cats – clarification regarding genetic testing

Abstract

The release of new DNA-based diagnostic tools has increased tremendously in companion animals. Over 70 different DNA variants are now known for the cat, including DNA variants in disease-associated genes and genes causing aesthetically interesting traits. The impact genetic tests have on animal breeding and health management is significant because of the ability to control the breeding of domestic cats, especially breed cats. If used properly, genetic testing can prevent the production of diseased animals, causing the reduction of the frequency of the causal variant in the population, and, potentially, the eventual eradication of the disease. However, testing of some identified DNA variants may be unwarranted and cause undo strife within the cat breeding community and unnecessary reduction of gene pools and availability of breeding animals. Testing for mucopolysaccharidosis Type VI (MPS VI) in cats, specifically the genetic testing of the L476P (c.1427T>C) and the D520N (c.1558G>A) variants in arylsulfatase B (ARSB), has come under scrutiny. No health problems are associated with the D520N (c.1558G>A) variant, however, breeders that obtain positive results for this variant are speculating as to possible correlation with health concerns. Birman cats already have a markedly reduced gene pool and have a high frequency of the MPS VI D520N variant. Further reduction of the gene pool by eliminating cats that are heterozygous or homozygous for only the MPS VI D520N variant could lead to more inbreeding depression effects on the breed population. Herein is debated the genetic testing of the MPS VI D520N variant in cats. Surveys from different laboratories suggest the L476P (c.1427T>C) disease-associated variant should be monitored in the cat breed populations, particularly breeds with Siamese derivations and outcrosses. However, the D520N has no evidence of association with disease in cats and testing is not recommended in the absence of L476P genotyping. Selection against the D520N is not warranted in cat populations. More rigorous guidelines may be required to support the genetic testing of DNA variants in all animal species.

Patterns of allele frequency differences among domestic cat breeds assessed by a 63K SNP array

“…Although the LYST and its severe consequences have been identified and described in cats (cited in [ 75 ]), we suspect that the large candidate region on Chr.A1 and LAMP1 more moderately contributes to the phenotypic characteristics of Ragdoll cats (e.g. light coat and eye colors) and explains its mucopolysaccharidoses [ 76 ].…”

Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats

“…Mucopolysaccharidosis Type VI (MPS VI), a lysosomal storage disease caused by a deficiency of Nacetylgalactosamine-4-sulfatase (4S), is another disease in which the roles of two variants, independently inherited in this case, have been under discussion (54). While the MPS VI variant c.1427T>C p.(L476P) of the ARSB gene is associated with severe disease (55), the c.1558G>A p. (D520N) variant of the ARSB gene is sometimes referred to as the "mild" type (56).…”

An overview of the current genetic and phenotypical selection strategies to reduce the prevalence of feline hypertrophic cardiomyopathy

“…Furthermore, there should be convincing evidence that this variant indeed causes the disease. Selection against a common variant that has no clinical significance can needlessly reduce the genetic variability of a breed (Lyons et al, 2016).…”

“…Both methods have their advantages, but also serious limitations. Furthermore, considerable controversy exists around the genetic tests available for feline HCM, and breeders are not always aware that these tests are only appropriate in specific breeds (Lyons, 2012;Lyons et al, 2016). In this review, a general overview is provided of why genetic diseases occur that often in companion animals.…”