UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory

Brazilian Terrier Genetic Tests

Tests Offered:
Mucopolysaccharidosis VII | Canine Multifocal Retinopathy 1 | Von Willebrand Disease I

Mucopolysaccharidosis VII (MPS VII)

Introduction

Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disease characterized by accumulation of glycosaminoglycans (amino sugars) within cells. Glycosaminoglycans are found in cells involved with development of bone, cartilage, tendons, corneas, skin and connective tissue, and in fluid that lubricates joints. Under normal conditions of cell metabolism, these amino sugars are broken down into simpler sugars by the beta-glucuronidase enzyme encoded by the gene β- glucuronidase (GUSB). Mutations in the GUSB gene disrupt production or activity of this enzyme leading to an accumulation of amino sugars that causes permanent cell damage. MPS VII disease has an early onset and is progressive. By one month of age, affected pups typically show shortened broad faces, low-set ears, and broad chests relative to unaffected littermates. By two months of age, corneal clouding is observed and differential development is apparent with affected dogs being roughly half the size of unaffected siblings. As the disease progresses, standing becomes difficult and joints become swollen and are easily dislocated. Additional clinical signs include cardiac abnormalities, tracheal narrowing, and glycosaminoglycans in the urine.

Two independent, breed-specific mutations in the GUSB gene result in MPS VII disease: c.866C>T in Brazilian Terriers (reported as MPS7bt) and c.497G>A in German Shepherd Dogs (reported as MPS7gs).  In both cases, the disease is inherited in an autosomal recessive fashion, which means that males and females are equally affected and that two copies of the defective gene are needed to cause MPSVII. Dogs with one normal and one affected gene (carriers) are normal and show no signs of the disease.

The Veterinary Genetics Laboratory offers genetic tests for MPS VII. Test results assist veterinarians with diagnosis of MPS VII and help breeders identify carriers among breeding stock to avoid producing affected dogs. Matings between carriers are expected to produce 25% of affected puppies.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Testing recommended for: Brazilian Terrier, German Shepherd Dog

Results reported as:

N/N

Normal - no copies of the MPSVII mutation

N/MPS7*

Carrier - 1 copy of the MPSVII mutation

MPS7/MPS7*

Affected - 2 copies of the MPSVII mutation

*Report will specify MPS7bt or MPS7gs according to breed and mutation present.

References:

Hytönen MK, Arumilli M, Lappalainen AK, Kallio H, Snellman M, Sainio K, Lohi H. (2012) A novel GUSB mutation in Brazilian terriers with severe skeletal abnormalities defines the disease as mucopolysaccharidosis VII. PLoS One 7:e40281.

Ray J, Bouvet A, DeSanto C, Fyfe JC, Xu D, Wolfe JH, Aguirre GD, Patterson DF, Haskins ME, Henthorn PS. (1998) Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine MPS VII, and retroviral vector-mediated correction of MPS VII cells. Genomics 48:248-253.

Canine Multifocal Retinopathy 1 (CMR1)

Introduction

Canine Multifocal Retinopathy 1 (CMR1) is an inherited eye disease caused by a mutation (c.73C>T) in the Bestrophin 1 gene that results in a shortened, dysfunctional protein. Affected dogs typically present with multiple, discrete circular areas of retinal detachment between 11 and 16 weeks of age. Fluid accumulates under the detached retina resulting in gray, tan, orange or pink “blisters” in the eye. Progression of retinal changes is slow, ceases by 1 year and does not lead to blindness. In some cases, the blisters appear to heal as the dog ages but vision loss has been reported. The disease is inherited in an autosomal recessive fashion thus two copies of the CMR1 mutation must be present to produce the disease. Breeding two carriers is predicted to produce 25% affected pups

The VGL offers a genetic test for the CMR1 mutation. Genetic screening helps breeders establish the genetic status of breeding stock and select mating pairs appropriately in order to reduce the risk of producing CMR1-affected offspring.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Testing recommended for: American Bulldog, American Bully, Aussiedoodle, Australian Koolie, Australian Shepherd, Brazilian Terrier, Bulldog, Bullmastiff, Cane Corso, Dogue de Bordeaux, French Bulldog, Great Pyrenees, Havanese, Koolie, Mastiff, Miniature American Shepherd, Miniature Australian Shepherd, Perro de Presa Canario, Shorty Bull, South African Boerboel, Toy Australian Shepherdherd Dog

Results reported as:

N/N

Normal - no copies of the CMR1 mutation

N/CMR1

Carrier - 1 copy of the CMR1 mutation; dog is normal

CMR1/CMR1

Affected - 2 copies of the CMR1 mutation; dog will develop multifocal retinopathy

References:

Gornik KR, Pirie CG, Duker JS, Boudrieau RJ. Canine multifocal retinopathy caused by a BEST1 mutation in a Boerboel. Vet Ophthalmol. 2013 Sep 3. [PubMed: 23998685]

Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One. 2016 Aug 15;11(8). [PubMed: 27525650]

Von Willebrand Disease I (vWD Type 1)

Introduction

Von Willebrand disease (vWD) is an inherited bleeding disorder resulting from a lack or reduced level of a normal blood clotting protein called von Willebrand factor (vWF). Disease presentation varies from asymptomatic to spontaneous hemorrhaging and prolonged bleeding after injury, surgery or giving birth. Furthermore, age of onset varies with some dogs only becoming obvious “bleeders” later in life. Without medical intervention, uncontrolled bleeding can result in death. Several genetic mutations that prevent normal functioning of vWF have been identified. These mutations are associated with different clinical bleeding disorders known as vWD Type 1, Type 2 and Type 3. 

vWD Type 1 is the most common bleeding disorder among dogs and is present in several breeds. The disorder is characterized by a low concentration of vWF in blood. While vWD Type 1 can cause serious bleeding problems, it is generally less severe than the other two types of vWD and can be alleviated by treatment. A mutation in vWF (c.7437G>A) is associated with vWD Type 1. This disorder is inherited as a dominant trait with incomplete penetrance, which means that not all dogs that have the vWF mutation will present clinical signs of the disease.

ORDER TEST KITS | PRICE LIST
Allow 5-10 business days for results.

Type 1 Testing recommended for: Australian Cobberdog, Barbet, Bernese Mountain Dog, Brazilian Terrier, Cardigan Welsh Corgi, Coton de Tulear, Doberman Pinscher, Drentsche Patrijshond, Dutch Partridge Dog, Dutch Shepherd, French Water Dog, German Pinscher, Havanese, Irish Red and White Setter, Irish Setter, Kerry Blue Terrier, Kromfohrländer, Manchester Terrier, Papillon, Pembroke Welsh Corgi, Phalene, Poodles, Doodle and Poo breeds, Stabyhoun, Toy Manchester Terrier, West Highland White Terrier

Results reported as:

N/N

Normal - No copies of vWF mutation associated with vWD Type 1.

N/vWF

1 copy of vWF mutation. Dog may be affected and may develop vWD Type 1.

vWF/vWF

2 copies of vWF mutation. Dog may be affected and may develop vWD Type 1.

References:

Brooks MB, Erb HN, Foureman PA, Ray K. (2001) von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers. Am J Vet Res 62(3):364-369.

Crespi JA, LS Barrientos, G Giovambattista. (2018) von Willebrand disease type 1 in Doberman Pinscher dogs: genotyping and prevalence of the mutation in the Buenos Aires region, Argentina. J Vet Diagn Investg 30(2):310-314.

Donner J, Kaukonen M, Anderson H, Moller F, Kyostila K, Sankari S, Hytonen M, Giger U, Lohi H. (2016) Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders. PLoS One 11(8). DOI:10.1371/journal.pone.0161005

Vos-Loohuis M, van Oost BA, Dangel C, Langbein-Detsch I, Leegwater PA. (2017) A novel VWF variant associated with type 2 von Willebrand disease in German Wirehaired Pointers and German Shorthaired Pointers. Anim Genet 48:493–496.

Rieger M, Schwarz HP, Turecek PL, Dorner F, van Mourik JA, Mannhalter C. (1998) Identification of mutations in the canine von Willebrand factor gene associated with type III von Willebrand disease. Thromb Haemost 80(2):332-337.

Venta PJ, Li J, Yuzbasiyan-Gurkan V, Brewer GJ, Schall WD. (2000) Mutation causing von Willebrand’s Disease in Scottish Terriers. J Vet Intern Med 14(1):10-19.

 

 
Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL