Spinal muscular atrophy (KDSR-related)

Gene: KDSR

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, KDSR gene: c.562G>A, p.(Ala188Thr), exon6, Chr.24.

Medical system: Muscular, neuromuscular

Breed: Brown Swiss

Age of onset of symptoms: At birth to within one week of birth.

The Brown Swiss cattle breed is a modern dairy breed whose genetics derived originally from multi-purpose Swiss animals.  Selection for dairy traits led to a loss of genetic diversity and to an increase in simple hereditary diseases including spinal muscular atrophy.  Spinal muscular atrophy is a neurodegenerative disease of Brown Swiss calves seen within the first week of birth. It involves progressive weakness, particularly of the hindlimbs, due to profound muscular atrophy.  Motor neuron and axonal swelling result in motor neuron degeneration and lead to the death of the affected animal within a few weeks of birth.  Molecular studies of affected calves identified a mutation in the KDSR gene as being responsible for the disease.  The KDSR gene codes for an enzyme important for the synthesis of glycosphingolipid molecules, themselves important in the structure and function of nerve cell membranes.  In a survey study of 1991 Brown Swiss animals, conducted in 2011, a carrier frequency of 9.2% was recorded for the KDSR mutation.  A DNA test is available that allows breeders to reduce mutation frequencies in their herds by selective breeding.  In doing so, care must be exercised not to compromise the genetic diversity of their animals.

References:

OMIA link: [2390-9913]

VanRaden PM, Olson KM, Null DJ, Hutchison JL. (2011) Harmful recessive effects on fertility detected by absence of homozygous haplotypes. J Dairy Sci 94:6153-61.  [pm/22118103]

Krebs S, Medugorac I, Röther S, et al. (2007) A missense mutation in the 3-ketodihydrosphingosine reductase FVT1 as candidate causal mutation for bovine spinal muscular atrophy. Proc Natl Acad Sci U S A 104:6746-51.  [pm/17420465]

Troyer D, Cash WC, Vestweber J, et al. (1993) Review of spinal muscular atrophy (SMA) in Brown Swiss cattle. J Vet Diagn Invest 5:303-6. [pm/8507715]

With contributions by: Zoé Raphaëlle Caron and Sophia Léger, Class of 2030, Faculty of Veterinary Medicine, University of Montreal.  (Translation: DWS).