Hydrocephalus, familial

Gene: B3GALNT2

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, B3GALNT2 gene; c.1423C>T, p.(475 STOP), exon12, chr.1.

Medical system: Neurologic, skeletal

Breeds: At birth.

Age of onset of symptoms: At birth.

Hydrocephalus, literally “water on the brain”, results when the natural production and flow of cerebrospinal fluid (CSF) within the ventricles of the brain are deregulated, leading to CSF accumulation, cranial extension, and pressure damage to brain structures. Hydrocephalus can have both genetic and environmental causes and is an occasional observation in several horse breeds. In the Friesian horse, a congenital hydrocephalus with autosomal recessive heredity is described that can result in stillbirths of the foal, dystocia in the mare or in cephalic malformations of the foal requiring euthanasia. Molecular studies revealed a mutation within the B3GALNT2 gene, a gene that normally codes for a glycosyltransferase enzyme that transfers galactose sugar groups to proteins to modify protein function. In a survey of 865 Friesen horses, a carrier (M/N) frequency of 17% was reported for the B3GALNT2 mutation. The availability of a DNA test for the mutation will help Friesian breeders in identifying carrier animals and enable them to eliminate the disease from their animals. Elimination of the mutation from the breed should be performed slowly over several generations so as not to create a genetic bottleneck with increased inbreeding coefficients for the breed.

References:

OMIA link: [0487-9796]

Kolb DS, Klein C. (2019) Congenital hydrocephalus in a Belgian draft horse associated with a nonsense mutation in B3GALNT2. Can Vet J 60:197-198. [pm/30705458]

Ayala-Valdovinos MA, Galindo-García J, Sánchez-Chiprés D, Duifhuis-Rivera T. (2017) Genotyping of friesian horses to detect a hydrocephalus-associated c.1423C>T mutation in B3GALNT2 using PCR-RFLP and PCR-PIRA methods: Frequency in stallion horses in México. Mol Cell Probes 32:69-71. [pm/38011345]

Ducro BJ, Schurink A, Bastiaansen JW, et al. (2015). A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC genomics, 16:761. [pm/26452345]

Contributed by: Mégan Dugas and Manar Zekhnini, Class of 2028, Faculty of Veterinary Medicine, University of Montreal.