The Paw Print Genetics Blog

The Veterinarian’s Corner- New Canine Genetic Disease Tests to Aid in Clinical Diagnosis

The Veterinarian’s Corner- New Canine Genetic Disease Tests to Aid in Clinical Diagnosis

To usher in 2022, Paw Print Genetics (PPG) has added 12 new canine disease and trait tests to expand upon the largest selection of canine genetic tests in the industry. However, because diseases seen in veterinary practice are not seen with equal frequency, here I will highlight five of the new test offerings for diseases that are among the most likely to be encountered in veterinary practice. 

Ataxia (Norwegian Buhund Type)1- Norwegian Buhund

Ataxia (Norwegian buhund type), also known as cerebellar ataxia, is an early-onset autosomal recessive neurological disease affecting the Norwegian buhund. Dogs inheriting two copies of the associated KCNIP4 gene mutation present between three and five months of age with progressive neurological disease. Initial clinical signs are consistent with cerebellar ataxia, including wide-based stance, hypermetria, head tremors, and truncal sway. As the disease progresses, dogs are eventually unable to stand or walk without falling. Cerebellar degeneration is a common histopathological finding in affected dogs and dramatic reductions in cerebellar KCNIP4 protein have been described. The speed of disease progression is variable, but affected dogs are often euthanized due to quality-of-life concerns.

In one study, 19% out of 146 apparently healthy Norwegian buhunds tested carried one copy of the KCNIP4 mutation suggesting that this mutation may be found in high frequency in the buhund’s relatively small population. 1 However, the exact frequency of this mutation in the overall breed population is unknown.

Glaucoma (Border Collie Type)2,3- Border Collie

Glaucoma (border collie type), also known as goniodysgenesis and glaucoma or primary closed-angle glaucoma (PCAG), is an autosomal recessive eye disease affecting border collies. Affected dogs display congenital malformations of the pectinate ligament, resulting in narrowing (or closure) of the iridocorneal angle and inadequate aqueous humor drainage. Dogs inheriting two copies of the associated OLFML3 gene mutation present at variable age with classic clinical signs of glaucoma, including ocular pain, squinting, tearing, redness, and excessive blinking. However, pectinate ligament dysplasia may also be identified in preclinical dogs via gonioscopy, prior to development of excessive intraocular pressure. As typical with glaucoma, long term elevations in intraocular pressure result in optic nerve damage and subsequent vision loss.

In one study, 6.8% of 103 border collies of unknown health status carried one copy of the OLFML3 gene mutation.2 In another study, 8.3% of 350 border collies of unknown health status were found to be carriers.3 However, the frequency of this mutation in the overall breed population is unknown.

Ichthyosis (Golden Retriever Type 2)4- Golden Retriever

Ichthyosis (golden retriever type 2) is an autosomal recessive, non-epidermolytic ichthyosis affecting the golden retriever, and is the second disease of this type identified in the breed. Dogs inheriting two copies of the associated ABHD5 gene mutation present early in life with white to gray, non-inflammatory skin scaling throughout the hair coat and concave surface of the pinnae. Skin on the abdomen may become hyperpigmented. Some severely affected puppies have been reported to display a swollen, tight appearance of the skin, skin resembling ‘cracked glass’, and deep cracks resulting in bleeding. However, full clinical descriptions of dogs affected with type 2 ichthyosis are limited.

It should be noted that a more common genetic mutation in the PNPLA1 gene is well known by breeders to cause a similar form of ichthyosis in golden retrievers (known as golden retriever type 1).5 Although ichthyosis type 2 is generally reported by breeders to be more severe than type 1, the severity of both types can vary by individual or blood line. Descriptions of dogs affected with both types of ichthyoses simultaneously are lacking.

The frequency of the ABHD5 mutation is unknown in the overall golden retriever population but is generally believed to be less common than the PNPLA1 mutation associated with ichthyosis (golden retriever type 1). Testing for both mutations is indicated for golden retrievers displaying clinical signs of ichthyosis. Humans with mutations in the ABHD5 gene are known to develop Chanarin-Dorfman syndrome; a syndrome marked by ichthyosis, dysfunction of lipid metabolism, and excessive lipid storage throughout various organs and tissues of the body. Similar dysfunction of lipid metabolism or storage have not yet been documented in dogs with ABHD5 gene mutations, however additional study is required to assess this potential risk.

Neuroaxonal Dystrophy (Rottweiler Type)6,7- Rottweiler

Neuroaxonal dystrophy (Rottweiler type) is a progressive autosomal recessive neurological disease affecting Rottweilers. Dogs inheriting two copies of the associated VPS11 gene mutation present before five years of age (and most commonly before two years) with a variety of neurological clinical signs including progressive ataxia, head tremors, incoordination, hypermetria, and nystagmus. Despite maintaining normal vision and pupillary light reflexes, affected dogs tend to display a decreased menace response during neurological exam. Histopathologic examinations of affected dogs reveal cerebellar atrophy, signs of noninflammatory neurodegeneration, and demyelinating lesions primarily located in regions associated with the sensory nervous system.

In one study, 4.6% of 281 Rottweilers tested were found to carry one copy of the VPS11 mutation.7 However, the frequency of this mutation in the overall Rottweiler population is unknown.

Recurrent Inflammatory Pulmonary Disease8- Rough Collie and Smooth Collie

Recurrent inflammatory pulmonary disease is an autosomal recessive disease affecting rough and smooth collies. Dogs inheriting two copies of the associated AKNA gene mutation present within the first few weeks of life with signs of inflammatory respiratory disease, including shallow, noisy breathing, nasal discharge, cough, and fever. Affected dogs respond favorably to treatment for respiratory infection, however clinical signs recur quickly upon cessation of therapy. Dogs can be maintained with medical therapy for many years despite continuing to have signs of respiratory disease throughout their lives. While the exact molecular cause of this condition is still undetermined, AKNA is known to encode a protein which plays a crucial role in immune system regulation. Although different in its etiology, this disease presents very similarly to primary ciliary dyskinesia and should be on a veterinarian’s list of differential diagnoses in cases of recurrent respiratory infection involving collies.

The frequency of the AKNA gene mutation in the overall collie population is unknown. Population screening for this mutation has only been described in a small subset of collies including dogs confirmed to be relatives to known affected dogs. In that study, 21% of 85 rough collies tested were carriers of one copy of the mutation. However, given the population studied, it is probable that the actual frequency of the mutation in the overall collie population is lower.

Contact Paw Print Genetics

If you have questions about how Paw Print Genetics can assist with genetic testing in your veterinary practice, please contact our knowledgeable geneticists and veterinarians at or give us a call during business hours (8 am to 5 pm Pacific time, Monday to Friday) at 509-483-5950.


  1. Jenkins CA, Kalmar L, Matiasek K, Mari L, Kyosila K, Lohi H, Schofield EC, Mellersh CS, De Risio L, Ricketts SL. Characterisation of canine KCNIP4: A novel gene for cerebellar ataxia identified by whole genome sequencing two affected Norwegian Buhund dogs. Mamm Genome. 2015 Feb;26(1-2):108-17. [PubMed: 31999692]
  2. Oliver JAC, Wright H, Massidda PA, Burmeister LM, Mellersh CS. A variant in OLFML3 is associated with pectinate ligament abnormality and primary closed‐angle glaucoma in Border Collies from the United Kingdom. Vet Ophthalmol. 2019 May 29. [PubMed: 31141290]
  3. Pugh CA, Farrell LL, Carlisle AJ, Bush SJ, Trejo-Reveles V, Matika O, de Kloet A, Walsh C, Bishop SC, Prendergast JGD, Schoenebeck JJ, Rainger J, Summers KM. Arginine to glutamine mutation in olfactomedin-like 3 (OLFML3) is a candidate for severe goniodysgenesis and glaucoma in the Border Collie dog breed. G3 (Bethesda). 2019 Mar 7;9(3):943-954. [PubMed: 30696701]
  4. Kiener S, Wiener D, Hopke K, Diesel A, Jagannathan V, Mauldin E, Casal M, Leeb T.  ABHD5 frameshift deletion in Golden Retrievers with ichthyosis, G3 Genes|Genomes|Genetics, 2021 [PubMed: 34791225]
  5. Grall A, Guaguère E, Planchais S, Grond S, Bourrat E, Hausser I, Hitte C, Le Gallo, M., Derbois C, Kim GJ, Lagoutte L, Degorce-Rubiales F, Radner FP, Thomas A, Küry S, Bensignor E, Fontaine J, Pin D, Zimmermann R, Zechner R, Lathrop M, Galibert F, André C, Fischer J. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet. 2012 Jan 15;44(2):140-7. [PubMed: 22246504]
  6. Chrisman CL, Cork LC, Gamble DA. Neuroaxonal dystrophy of Rottweiler dogs. J Am Vet Med Assoc. 1984 Feb 15;184(4):464-7. PubMed: 6698879 [PubMed: 6698879]
  7. Lucot KL, Dickinson PJ, Finno CJ, Mansour TA, Letko A, Minor KM, Mickelson JR, Drogemuller C, Brown CT, Bannasch DL. A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs. G3 (Bethesda). 2018 Jul 31;8(8):2773-2780. doi: 10.1534/g3.118.200376. PubMed: 29945969 [PubMed: 29945969]
  8. Hug P, Anderegg L, Kehl A, Jagannathan V, Leeb T. AKNA Frameshift Variant in Three Dogs with Recurrent Inflammatory Pulmonary Disease. Genes (Basel). 2019 Jul 26;10(8). pii: E567. [PubMed: 31357536]

*Photo Credit: Unaltered Photo ‘Teddy’ courtesy of Eric Drost via Flickr Creative Commons license