Help us fight disease and injury in animals

Cone -Rod Dystrophy form of Progressive Retinal Atrophy in the Wire-Haired Dachshund (Miniature and Standard)

Progressive retinal atrophy (PRA) is a disease of the retina. This tissue, located inside the back of the eye, contains specialized cells called photoreceptors that absorb the light focused on them by the eye’s lens, and convert this light into electrical nerve signals which are then interpreted by the brain as vision. These photoreceptors are divided into two groups; the cones which aid bright light and colour vision, and the rods which facilitate low light or night vision. PRA is an inherited condition and occurs in many different forms across a wide variety of dog breeds, resulting in the loss of vision, and more often leading to blindness.

Unfortunately, at this time there is no treatment or cure for PRA. Clinical diagnosis should be made by a veterinary ophthalmologist using the methods of indirect ophthalmoscopy and/or electroretinography, although this can only observe affected dogs after symptoms have developed and will never detect the symptomless carriers.

Cone-rod dystrophy (CRD) is a type of PRA which first affects the cones in the retina, so initially results in day blindness for sufferers, and then the rods begin degenerating secondarily. Researchers in Norway, Sweden and the USA have combined to identify a change (mutation) in a gene called nephroretinin (NPHP4) that causes early-onset CRD. They compared 13 different sets of Standard Wire-Haired Dachshund siblings (one sibling with CRD and one without). The NPHP4 gene was found to be shorter in all of the clinically PRA affected dogs. Within the group of  dogs used in their research, the age of initial CRD (NHPH4) onset for affected dogs varied between 10 months to 3 years, with complete retinal atrophy observed by 6 years old.

The mutation, or change to the structure of the gene, probably occurred spontaneously in a single dog but once in the population has been inherited from generation to generation like any other gene. The disorder shows an autosomal recessive mode of inheritance, and therefore two copies of the defective gene (one inherited from each parent) have to be present for a dog to be clinically affected by the disease.

In a recent research study at the Animal Health Trust, we have confirmed that the NHPH4 mutation also exists in Miniature Wire-Haired Dachshunds.

Our research shows that the frequency of the NHPH4 mutation in Miniature Wire-Haired Dachshunds is 3.1% - implying that the number of carriers in the UK population of Miniature Wire-Haired Dachshunds may approach 6 in 100 - although it has not currently been shown that the NHPH4 mutation causes PRA in Miniature Wire-Haired Dachshunds. We are offering the test now to breeders of Standard Wire-Haired Dachshunds and to breeders of Miniature Wire-Haired Dachhunds who have the NHPH4 mutation in their lines.

At the Animal Health Trust, we have already shown that the gene for another form of PRA, cord1, is also present in Miniature Wire-Haired Dachshunds and we do offer a DNA test for this form of PRA. Breeders should ensure, by taking appropriate veterinary advice, that they are requesting the correct DNA test.

The CRD test is available now and information on submitting samples is given below. Owners will be sent results identifying their dog as belonging to one of three categories:-

CLEAR: the dog has 2 copies of the normal gene and will neither develop this form of PRA, nor pass a copy of the CRD (NPHP4) mutation to any of its offspring.

CARRIER: the dog has one copy of the normal gene and one copy of the mutant gene that causes that causes the CRD (NPHP4) form of PRA in Standard Wire -haired Dachshunds. It will not develop the condition but will pass on the CRD (NPHP4) mutation to 50% (on average) of its offspring.

AFFECTED: Standard Wire-Haired Dachshunds having two copies of the CRD (NPHP4) mutation are highly likely to develop this cone-rod dystrophy form of PRA at some stage during their lifetime assuming they live to an appropriate age. Affected dogs will pass on a copy of the mutation to any offspring.

Carriers may still be bred to clear dogs. On average, 50% of such a litter will be clear and 50% carriers; there can be no genetically affected dog produced from such a mating. Pups which will be used for breeding can themselves be DNA tested to determine whether they are clear or carrier.

A description of the research into CRD in Standard Miniature Wire-Haired Dachshunds underlying this test can be found in:
Wiik,A.C, Wade,C., Biagi,T., Ropstad,E-O, Bjerkas,E., Lindblad-Toh,K. and Lingaas,F. (2008) A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund.Genome Res. 18 1415–1421.

Samples submitted should be cheek swabs (a non-invasive sampling method) obtained from the Animal Health Trust. Samples should be sent together with a completed DNA Testing form for each sample to Genetic Services, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU.  The price of the test is £54, which includes both VAT and the cost of the mouth swab sampling kit.

Kits for taking cheek swabs are available via our webshop.

Further information can be obtained by e-mailing dnatesting@aht.org.uk or swabrequest@aht.org.uk, or by phoning +44 (0)1638 555621