PennHIP
Canine Eye Registration Foundation (CERF)
NOTICE: After nearly 30 years of working towards the elimination of heritable eye disease in dogs, The Canine Eye Registration Foundation (CERF) will stop accepting new registrations for the CERF registry on June 15, 2014. Our on-line registry will continue to be available for approximately the next year after which CERF records will be able via the OFA website. CERF would like to thank all of our breeders and dog lovers for their continued support over these many years. Please direct any questions and/or concerns that you may have to [email protected].
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CERF was founded by a group of concerned purebred owners and breeders with the goal of eliminating heritable eye diseases in purebred dogs through registration, research, and education.
CERF Categories We use these categories to let you and potential owners know there was a diagnosis and where it was located. These codes are listed on the back of the CERF Certificate.
http://web.vmdb.org/home/
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CERF was founded by a group of concerned purebred owners and breeders with the goal of eliminating heritable eye diseases in purebred dogs through registration, research, and education.
CERF Categories We use these categories to let you and potential owners know there was a diagnosis and where it was located. These codes are listed on the back of the CERF Certificate.
http://web.vmdb.org/home/
Eye Certification Registry (ECR)
The purpose of the OFA Eye Certification Registry (ECR) is to provide breeders with information regarding canine eye diseases so that they may make informed breeding decisions in an effort to produce healthier dogs. ECR certifications will be performed by board certified (ACVO) veterinary ophthalmologists. Regardless of whether owners submit their ECR exam forms to the OFA for “certification,” all ECR exam data is collected for aggregate statistical purposes to provide information on trends in eye disease and breed susceptibility. Clinicians and students of ophthalmology as well as interested breed clubs and individual breeders and owners of specific breeds will find this useful.
http://www.offa.org/eye_overview.html
http://www.offa.org/eye_overview.html
Progressive Retinal Athrophy/Progressive Rod-Code Degeneration (PRA/PRCD)
Late form of Progressive Retinal Athrophy, called PRA-prcd (progressive rod-code degeneration), is just one of all retinal defects. Rods degenerate at first. Affected dogs become night-blind. This is very often the first symptom that dog owners recognize. Dogs usually have poor sense of directions and they crash in things. Pupil is widely open even when direct
ray of light hit the eye (dogs have shining eyes in pictures). Later, cones start degenerating. Final disease symptoms are cataracts and total blindness.
PRA-prcd defect arises after normal photoreceptors development. Degree of degeneration differs in parts of retina. Lower retina part is affected sooner and more than upper part (this is not obvious by ophthalmology examination). Disease recognition should be made during dog adolescence. Clinical diagnosis by electroretinogram (ERG) or opthalmoscopy of PRA-prcd can be difficult. ERG identifies affected animals sooner than opthalmoscopy.
PRA-prcd is a hereditary disease. Causal mutation G1298A in ninth canine chromosome (CFA9) PRA-prcd was recognized. This mutation is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P genotype
only. The dogs with P/N genotype are considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be
recommended.
The disease cannot be cured, but it is possible to eliminate it through genetic testing of litters and proper choice of parents.
DNA test is an advisable alternative to the clinical examination. The test can be performed only once in life of the animal, because the genotype does not change with age.
ray of light hit the eye (dogs have shining eyes in pictures). Later, cones start degenerating. Final disease symptoms are cataracts and total blindness.
PRA-prcd defect arises after normal photoreceptors development. Degree of degeneration differs in parts of retina. Lower retina part is affected sooner and more than upper part (this is not obvious by ophthalmology examination). Disease recognition should be made during dog adolescence. Clinical diagnosis by electroretinogram (ERG) or opthalmoscopy of PRA-prcd can be difficult. ERG identifies affected animals sooner than opthalmoscopy.
PRA-prcd is a hereditary disease. Causal mutation G1298A in ninth canine chromosome (CFA9) PRA-prcd was recognized. This mutation is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P genotype
only. The dogs with P/N genotype are considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be
recommended.
The disease cannot be cured, but it is possible to eliminate it through genetic testing of litters and proper choice of parents.
DNA test is an advisable alternative to the clinical examination. The test can be performed only once in life of the animal, because the genotype does not change with age.
Multi Drug Resistance (MDR1)
Many herding breed dogs have a genetic predisposition to adverse drug reactions involving over a dozen different drugs. The most serious adverse drug reactions involve several antiparasitic agents (ivermectin, milbemycin and related drugs),
the antidiarrheal agent loperamide (Imodium), and several anticancer drugs (vincristine, doxorubicin, others). These drug sensitivities result from a mutation in the multidrug resistance gene (MDR1 gene). At Washington State University's College of Veterinary Medicine you can test your dog for multidrug sensitivity and prevent serious adverse drug reactions.
Drugs that have been documented to cause problems in dogs with the MDR1
mutation include:
Drugs that are known to be pumped out of the brain by the protein that the MDR1 gene is responsible for producing but appear to be safely tolerated by dogs with the MDR1 mutation:
Cyclosporin (immunosuppressive agent). While we know that cyclosporin is pumped by P-glycoprotein (the protein encoded by the MDR1 gene), we have not documented any increased sensitivity to this drug in dogs with the mutation compared to "normal" dogs. Therefore, we do not recommend altering the dose of cyclosporin for dogs with the MDR1 mutation, but we do recommend therapeutic drug monitoring.
the antidiarrheal agent loperamide (Imodium), and several anticancer drugs (vincristine, doxorubicin, others). These drug sensitivities result from a mutation in the multidrug resistance gene (MDR1 gene). At Washington State University's College of Veterinary Medicine you can test your dog for multidrug sensitivity and prevent serious adverse drug reactions.
Drugs that have been documented to cause problems in dogs with the MDR1
mutation include:
Drugs that are known to be pumped out of the brain by the protein that the MDR1 gene is responsible for producing but appear to be safely tolerated by dogs with the MDR1 mutation:
Cyclosporin (immunosuppressive agent). While we know that cyclosporin is pumped by P-glycoprotein (the protein encoded by the MDR1 gene), we have not documented any increased sensitivity to this drug in dogs with the mutation compared to "normal" dogs. Therefore, we do not recommend altering the dose of cyclosporin for dogs with the MDR1 mutation, but we do recommend therapeutic drug monitoring.
HEREITARY CATARACTS (HC or HSF4)
Cataracts are a clouding of lens of the eye caused by a breakdown of tissue in the eye. This generally results in an inability to see clearly, and can cause total blindness. In canines, cataracts are often familial; this type is known as Hereditary Cataracts. A mutation in the HSF4 gene causes this type of cataracts in several breeds of dogs. In this case, the dog is typically affected bilaterally, in that both eyes are affected by the cataracts. The cataracts associated with HSF4 also occur in the posterior region of the lens. They usually begin small and grow progressively, though the speed of growth is highly variable. Some cataracts will grow so slowly that the dog's vision remains relatively clear, while others will grow such that the dog will quickly go blind. Corrective surgery is possible, though it is costly and is not always effective.
One HSF4 mutation causes the recessive form of Hereditary Cataracts in Boston Terriers, Staffordshire Bull Terriers, and French Bulldogs. Because it is recessive, a dog must have two copies of this mutation to experience this form of cataracts. This mutation is only responsible for early-onset hereditary cataracts, which typically occur between 12 months and 3 years of age in Staffordshires, and between 2-3 years in Boston Terriers. Boston Terriers can also be afflicted by late-onset hereditary cataracts; however, the HSF4 gene mutation is not responsible for that particular form of cataracts. The causative gene for Late-onset Hereditary Cataracts in Boston Terriers has not been determined at this time.
A separate mutation of the HSF4 gene is responsible for Hereditary Cataracts in Australian Shepherds. This mutation affects Aussies differently, in that the disease is dominant, but not completely penetrant. This means that only one copy of the mutation is necessary to predispose a dog to the disease, however, incomplete penetrance means that a dog that has this mutation will not always develop HC. Research suggests that the mutation makes a dog 12 times more likely to develop posterior bilateral cataracts at some point in their lifetime. It is likely that a secondary gene interaction occurs in the small percentage of dogs possessing the HC mutation but do not develop cataracts, however, this interaction is not yet know.
It should also be noted that not all cataracts are hereditary. Cataracts can also be caused by old age or injury. Also, cataracts that occur in different regions of the lens can also be familial, however, are not attributed to this gene mutation.
Breeds Affected by Hereditary Cataracts (HC)
Australian Shepherds, Boston Terriers, French Bulldogs, Staffordshire Bull Terriers
HC/HC
AFFECTED: The dog carries two copies of the mutant gene and is homozygous for Hereditary Cataracts. The dog is affected by HSF4-Hereditary Cataracts, and will always pass on a copy of the mutated gene to its offspring.
n/HC
CARRIER: Both the normal and mutant copies of the gene detected. Dog is a carrier for Hereditary Cataracts, and can pass on a copy of the defective gene to any offspring.
n/n
CLEAR: Dog tested negative for the Hereditary Cataract gene mutation, and will not pass on the defective gene to its offspring.
One HSF4 mutation causes the recessive form of Hereditary Cataracts in Boston Terriers, Staffordshire Bull Terriers, and French Bulldogs. Because it is recessive, a dog must have two copies of this mutation to experience this form of cataracts. This mutation is only responsible for early-onset hereditary cataracts, which typically occur between 12 months and 3 years of age in Staffordshires, and between 2-3 years in Boston Terriers. Boston Terriers can also be afflicted by late-onset hereditary cataracts; however, the HSF4 gene mutation is not responsible for that particular form of cataracts. The causative gene for Late-onset Hereditary Cataracts in Boston Terriers has not been determined at this time.
A separate mutation of the HSF4 gene is responsible for Hereditary Cataracts in Australian Shepherds. This mutation affects Aussies differently, in that the disease is dominant, but not completely penetrant. This means that only one copy of the mutation is necessary to predispose a dog to the disease, however, incomplete penetrance means that a dog that has this mutation will not always develop HC. Research suggests that the mutation makes a dog 12 times more likely to develop posterior bilateral cataracts at some point in their lifetime. It is likely that a secondary gene interaction occurs in the small percentage of dogs possessing the HC mutation but do not develop cataracts, however, this interaction is not yet know.
It should also be noted that not all cataracts are hereditary. Cataracts can also be caused by old age or injury. Also, cataracts that occur in different regions of the lens can also be familial, however, are not attributed to this gene mutation.
Breeds Affected by Hereditary Cataracts (HC)
Australian Shepherds, Boston Terriers, French Bulldogs, Staffordshire Bull Terriers
HC/HC
AFFECTED: The dog carries two copies of the mutant gene and is homozygous for Hereditary Cataracts. The dog is affected by HSF4-Hereditary Cataracts, and will always pass on a copy of the mutated gene to its offspring.
n/HC
CARRIER: Both the normal and mutant copies of the gene detected. Dog is a carrier for Hereditary Cataracts, and can pass on a copy of the defective gene to any offspring.
n/n
CLEAR: Dog tested negative for the Hereditary Cataract gene mutation, and will not pass on the defective gene to its offspring.
Collie Eye Anomaly / Choroidal Hypoplasia (CEA/CH)
Collies share Collie Eye Anomaly (CEA) with several other breeds – it’s not just a problem for collies. CEA is more technically known as Choroidal Hypoplasia (CH). It is a recessively inherited eye disorder that causes abnormal development of the choroid - an important layer of tissue under the retina of the eye. This disease is seen most frequently in U.S. collies, but also worldwide in Rough and Smooth Collies, Border Collies, Australian Shepherds, Lancashire Heelers, and Shetland Sheepdogs. Since the choroid layer does not develop normally from the start, the primary abnormality can be diagnosed at a very young age. Regrettably, there is no treatment or cure for CEA.
The symptoms and signs – the clinical phenotype – can vary greatly among affected dogs within one breed, between parent and offspring and even within a litter. This creates a difficult situation for the breeder. Learning about the genetic cause and the course of the disease will help you understand how to manage it better and eventually avoid it altogether with genetic testing.
The primary problem is choroidal hypoplasia (CH). There is under-development (hypoplasia) of the eye tissue layer called the choroid. The choroid appears pale and thin, almost transparent, and the blood vessels of the choroid can easily be recognized in those “thin” areas. The ophthalmologist, looking at the back of the eye (the fundus) with an ophthalmoscope, typically will see an area of choroidal thinning that appears like a “window” to the underlying vessels and sclera.
MILD disease: Mild disease is very common in U.S. collies and is present in the other breeds named above. It is easily recognizable on careful ophthalmologic examination as early as 5 to 8 weeks of age. The lesion appears as an area
lateral (temporal) to the optic disc with reduction or absence of pigment so that the underlying vessels of the choroid are seen. The choroidal vessels may be reduced in number and of abnormal shape. The underlying white sclera might
also be visible. Once the retina changes to its adult color around 3 months of age, the normal pigment sometimes masks the changes in the choroid (so-called “go normal” – read more below). In mildly affected dogs, choroidal thinning is
the only detectable abnormality and the dog retains normal vision throughout life. However, dogs with mild disease can produce severely affected offspring.
(The eye anomaly "merle” can be confused with choroidal hypoplasia, primarily in dogs from merle to merle breeding and whose coat color is whiter than their littermates. Although both conditions are inherited, can occur in the same breed and exhibit a range of fundus anomalies, there are sufficient dissimilarities for the ophthalmologist to make the distinction.)
SEVERE disease: In severely affected dogs, approximately 25% of dogs with CEA/CH, there are related problems with the
health of the eye that can result in serious vision loss in some cases. Colobomas are seen at and near the optic nerve head as outpouchings or “pits” in the eye tissue layers. Colobomas can lead to secondary complications such as partial or complete retinal detachments and/or growth of new but abnormal blood vessels with hemorrhage – bleeding inside the eye. This happens in 5-10% of dogs with CEA/CH, generally by 2 years of age, and can affect either one or both eyes. Complications of severe disease can lead to vision loss, although this disorder only rarely threatens total blindness.
CEA/CH is not progressive in the usual sense. The essential features, choroidal hypoplasia and coloboma, are congenital
– the abnormalities develop as the eye develops. These features are also stationary once ocular development is complete around 8-12 weeks of life. Retinal detachments and/or aberrant vessel formation can be congenital or develop later, in general only in eyes with colobomas.
Based on research done jointly by scientists at Cornell University and at The Fred Hutchinson Cancer Research Center, BOTH the mild and severe forms of CEA/CH disease now are proven to result from the exact same gene and mutation in ALL of the affected breeds named above. This disease gene is located on canine chromosome number 37 and the disease-causing mutation has been identified. The mutation acts like a RECESSIVE mutation. That means, both parents of an affected dog must have at least one copy of the mutation and both parents must have passed a copy of the mutation to
the offspring. The affected dog is HOMOZYGOUS RECESSIVE – that is, both copies of the gene are mutant. ALL dogs that are homozygous recessive affected will show at least the mild form of the disease. ALL affected dogs, regardless of the
actual severity of the lesions, are homozygous for the same mutant gene.
(A dog with one mutant copy and one normal copy of the CEA/CH gene is a carrier – is heterozygous. A dog with two copies of the normal CEA/CH gene is homozygous normal.)
Expected Results of Breeding Strategies for Inherited Recessive Diseases
Normal x Normal = 100% Normal
Normal x Carrier = 50% Normal, 50% Carriers
Normal x Affected = 100% Carriers
Carrier x Carrier = 25% Normal, 50% Carriers, 25% Affected
Carrier x Affected = 50% Carriers, 50% Affected
Affected x Affected = 100% Affected
The symptoms and signs – the clinical phenotype – can vary greatly among affected dogs within one breed, between parent and offspring and even within a litter. This creates a difficult situation for the breeder. Learning about the genetic cause and the course of the disease will help you understand how to manage it better and eventually avoid it altogether with genetic testing.
The primary problem is choroidal hypoplasia (CH). There is under-development (hypoplasia) of the eye tissue layer called the choroid. The choroid appears pale and thin, almost transparent, and the blood vessels of the choroid can easily be recognized in those “thin” areas. The ophthalmologist, looking at the back of the eye (the fundus) with an ophthalmoscope, typically will see an area of choroidal thinning that appears like a “window” to the underlying vessels and sclera.
MILD disease: Mild disease is very common in U.S. collies and is present in the other breeds named above. It is easily recognizable on careful ophthalmologic examination as early as 5 to 8 weeks of age. The lesion appears as an area
lateral (temporal) to the optic disc with reduction or absence of pigment so that the underlying vessels of the choroid are seen. The choroidal vessels may be reduced in number and of abnormal shape. The underlying white sclera might
also be visible. Once the retina changes to its adult color around 3 months of age, the normal pigment sometimes masks the changes in the choroid (so-called “go normal” – read more below). In mildly affected dogs, choroidal thinning is
the only detectable abnormality and the dog retains normal vision throughout life. However, dogs with mild disease can produce severely affected offspring.
(The eye anomaly "merle” can be confused with choroidal hypoplasia, primarily in dogs from merle to merle breeding and whose coat color is whiter than their littermates. Although both conditions are inherited, can occur in the same breed and exhibit a range of fundus anomalies, there are sufficient dissimilarities for the ophthalmologist to make the distinction.)
SEVERE disease: In severely affected dogs, approximately 25% of dogs with CEA/CH, there are related problems with the
health of the eye that can result in serious vision loss in some cases. Colobomas are seen at and near the optic nerve head as outpouchings or “pits” in the eye tissue layers. Colobomas can lead to secondary complications such as partial or complete retinal detachments and/or growth of new but abnormal blood vessels with hemorrhage – bleeding inside the eye. This happens in 5-10% of dogs with CEA/CH, generally by 2 years of age, and can affect either one or both eyes. Complications of severe disease can lead to vision loss, although this disorder only rarely threatens total blindness.
CEA/CH is not progressive in the usual sense. The essential features, choroidal hypoplasia and coloboma, are congenital
– the abnormalities develop as the eye develops. These features are also stationary once ocular development is complete around 8-12 weeks of life. Retinal detachments and/or aberrant vessel formation can be congenital or develop later, in general only in eyes with colobomas.
Based on research done jointly by scientists at Cornell University and at The Fred Hutchinson Cancer Research Center, BOTH the mild and severe forms of CEA/CH disease now are proven to result from the exact same gene and mutation in ALL of the affected breeds named above. This disease gene is located on canine chromosome number 37 and the disease-causing mutation has been identified. The mutation acts like a RECESSIVE mutation. That means, both parents of an affected dog must have at least one copy of the mutation and both parents must have passed a copy of the mutation to
the offspring. The affected dog is HOMOZYGOUS RECESSIVE – that is, both copies of the gene are mutant. ALL dogs that are homozygous recessive affected will show at least the mild form of the disease. ALL affected dogs, regardless of the
actual severity of the lesions, are homozygous for the same mutant gene.
(A dog with one mutant copy and one normal copy of the CEA/CH gene is a carrier – is heterozygous. A dog with two copies of the normal CEA/CH gene is homozygous normal.)
Expected Results of Breeding Strategies for Inherited Recessive Diseases
Normal x Normal = 100% Normal
Normal x Carrier = 50% Normal, 50% Carriers
Normal x Affected = 100% Carriers
Carrier x Carrier = 25% Normal, 50% Carriers, 25% Affected
Carrier x Affected = 50% Carriers, 50% Affected
Affected x Affected = 100% Affected
Cone Degeneration (CD)
The “CD” test is a DNA based test that provide a method to unequivocally identify Cone Degeneration Disease (CD) in the German Shorthaired Pointer, Alaskan Malamute and Australian Shepherds. Although the disease is rare in general, within an affected line it is important to control the gene frequency so as to prevent producing puppies affected with the disease. The mutations causing CD in these two breeds occur in the same gene (CNGB3) but are distinct mutations and arose separately.
CD disease causes day blindness due to degeneration of the retinal “cones” – cone-shaped cells in the retina that respond primarily to bright daylight. CD can be diagnosed in the early weeks of the affected dog’s life. Between 8 and 12 weeks of age, when retinal development is normally completed in dogs, signs of vision problems are noticeable. The pups become day-blind and are photophobic – meaning that exposure to bright light is irritating or even painful. The pup will shun brightly-lit areas. Vision in dim light remains normal. The retina of the affected dog initially appears normal when examined by an ophthalmologist and initially the ERG (electroretinogram) recording is normal. However, the ERG response from the degenerating cones declines with age and is non-recordable in the mature CD-affected dog.
In contrast to PRA (Progressive Retinal Atrophy), which is the more common type of retinal disease in many dog breeds,
CD does not affect night vision. A second type of cell in the retina, the “rods” – rod-shaped cells that respond primarily to dim light and detect movement – are not involved in this disease. The CD-affected dog keeps the ability to see at night or in dimly-lit areas.
Just as PRA is the canine version of human RP (retinitis pigmentosa), CD is the canine version of the human genetic
disease achromatopsia – total color blindness and day-blindness. Another name for day blindness is “hemerolopia.” Exciting gene therapy research aimed at correcting this condition (in dogs as a model for human disease) is currenty being conducted at the University of Pennsylvania.
Reliable identification of dogs that do not carry disease genes is the key to controlling autosomal recessive diseases. The "genetically clear," "noncarriers" or, more formally, "homozygous normals," such dogs can pass only the normal gene on to all their pups - which means that none of their pups can ever be affected with CD. These "clear" dogs can be bred to any mate, even to a CD-affected German Shorthaired Pointer, which may be a desirable breeding prospect for other reasons.
CD disease causes day blindness due to degeneration of the retinal “cones” – cone-shaped cells in the retina that respond primarily to bright daylight. CD can be diagnosed in the early weeks of the affected dog’s life. Between 8 and 12 weeks of age, when retinal development is normally completed in dogs, signs of vision problems are noticeable. The pups become day-blind and are photophobic – meaning that exposure to bright light is irritating or even painful. The pup will shun brightly-lit areas. Vision in dim light remains normal. The retina of the affected dog initially appears normal when examined by an ophthalmologist and initially the ERG (electroretinogram) recording is normal. However, the ERG response from the degenerating cones declines with age and is non-recordable in the mature CD-affected dog.
In contrast to PRA (Progressive Retinal Atrophy), which is the more common type of retinal disease in many dog breeds,
CD does not affect night vision. A second type of cell in the retina, the “rods” – rod-shaped cells that respond primarily to dim light and detect movement – are not involved in this disease. The CD-affected dog keeps the ability to see at night or in dimly-lit areas.
Just as PRA is the canine version of human RP (retinitis pigmentosa), CD is the canine version of the human genetic
disease achromatopsia – total color blindness and day-blindness. Another name for day blindness is “hemerolopia.” Exciting gene therapy research aimed at correcting this condition (in dogs as a model for human disease) is currenty being conducted at the University of Pennsylvania.
Reliable identification of dogs that do not carry disease genes is the key to controlling autosomal recessive diseases. The "genetically clear," "noncarriers" or, more formally, "homozygous normals," such dogs can pass only the normal gene on to all their pups - which means that none of their pups can ever be affected with CD. These "clear" dogs can be bred to any mate, even to a CD-affected German Shorthaired Pointer, which may be a desirable breeding prospect for other reasons.
Canine Multi-focal Retinopathy (CMR)
The CMR test is a DNA-based test that accurately diagnoses multi-focal retinopathy occurring in Australian Shepherds, Cane Corsos, Mastiffs, Great Pyrenees, Coton de Tulear, Lapponian Herders and Perro de Presa Canarios. The test also detects CARRIERS of this condition and clears dogs that are genetically NORMAL. Canine Multi-focal Retinopathy (CMR) is a recently identified recessively inherited eye disease known so far to affect the Mastiffs (English, Bullmastiff, French mastiff or Dogue de Bordeaux), Australian Shepherds, Cane Corsos, Perro de Presa Canarios, Great Pyrenees and Coton de Tulear. Early clinical studies in 1998 by Dr. Bruce Grahn at the University of Saskatchewan, Canada, first described CMR in the Great Pyrenees. The condition observed in each of the named breeds at an ophthalmologist’s exam includes numerous distinct (i.e. multi-focal), roughly circular patches of elevated retina with accumulation of material that produces gray-tan-pink colored lesions. These lesions, looking somewhat like blisters, vary in location and size, although typically they are present in both eyes of the affected dog.Discrete areas of tapetal hyper-reflectivity might also be seen.
The disease generally develops in young dogs before 4 months and might progress slowly, might appear to heal, or might even appear and then go away again. Some dogs affected with CMR do not show clinical symptoms of disease until later in life. The modifiers of CMR disease are a subject of research interest. Some lesions disappear with no remaining sign, while some lesions leave a wrinkled area – a fold. Some leave the lasting lesion of a blister formation. Most dogs exhibit no noticeable problem with vision despite their abnormal appearing retinas. And in almost all cases, CMR does not progress significantly over time. The disease seems to have a consistent pattern among the breeds identified so far, although lesions in the Coton de Tulear are often more serious and seem to remain longer than in some of the other CMR-affected breeds. In rare severe cases, the clinical diagnosis could be confused with progressive retinal atrophy (PRA). The full range of clinical symptoms will learned as more dogs are tested for their genetic status.
The clinical presentation and pathology of CMR closely resembles lesions of “Best vitelliform dystrophy”, a human disease with variable clinical expression but usually with serious affects on central vision. Identification of the gene mutation responsible for CMR was based on these similarities. A mutation in the human VMD2 gene – Vitelliform Macular Dystrophy 2 Gene – causes dominantly inherited human Best Disease. Analysis of the canine version of the VMD2 gene indicates that mutations in it cause CMR as a recessively inherited canine condition. The normal form of the VMD2 gene produces a protein named “bestrophin”. The bestrophin protein assembles, in the cells of the retinal pigment epithelium, in
a group of four or five units that form a pore through which chloride ions pass.
Our current understanding is that CMR is inherited in an autosomal recessive pattern. This means the gene mutation responsible for CMR is located on an autosome (that is, a chromosome that is not a sex chromosome) and CMR disease results when the gene mutation is passed to the offspring by both the mother and the father. It should be noted that the human disease that mirrors CMR in dogs is an autosomal dominant disease with incomplete penetrance. This means that sometimes, but not always, only one copy of the disease gene needs to be present in order for the disease to be observed clinically. At this point CMR in dogs is NOT considered to be an autosomal dominant disease however as more animals are characterized genetically with the CMR test, it is possible that we will find a similar form of inheritance as is seen in humans.
There is complete concordance of the mutation with the disease among affected dogs in the Mastiffs, Great Pyrenees, Australian Shepherds, Coton de Tulear and Lapponian Herders. However, retinal dysplasia described in other breeds, for example in Labradors, Samoyeds or English Springer Spaniels, is very distinct in comparison to CMR and these conditions are not caused by the CMR mutation. Due to the abnormal appearance of the CMR-affected retina, CERF, ACVO, ECVO and other ophthalmologist’s eye exam reports typically record these multi-focal lesions as “retinal dysplasia” or “retinal folds”, to denote a defect in formation of the retina. Such findings might disqualify the dog from breeding. Presently CERF
doesn’t list CMR as a specific condition, but does fail a dog for “retinal dysplasia/retinopathy – folds, detached.”
The genetic test for CMR is valuable for identifying the cause of a retinal deformation. Given the exact genetic diagnosis, the owner can be reassured that there probably will be little or no vision loss due to this condition. All the same, future cases of the condition can be prevented using the CMR test as an information tool for breeding Genetic Testing:
An exact diagnosis of this eye condition can be difficult. Definitive clinical diagnosis might even change due to the changing appearance of the retina as the dog ages. The CMR genetic test solves this problem immediately since presence of the CMR gene mutation is detected by testing a DNA sample. This result gives the owner immediate diagnostic information and aides in making decisions for the affected dog and for breeding strategies.
The disease generally develops in young dogs before 4 months and might progress slowly, might appear to heal, or might even appear and then go away again. Some dogs affected with CMR do not show clinical symptoms of disease until later in life. The modifiers of CMR disease are a subject of research interest. Some lesions disappear with no remaining sign, while some lesions leave a wrinkled area – a fold. Some leave the lasting lesion of a blister formation. Most dogs exhibit no noticeable problem with vision despite their abnormal appearing retinas. And in almost all cases, CMR does not progress significantly over time. The disease seems to have a consistent pattern among the breeds identified so far, although lesions in the Coton de Tulear are often more serious and seem to remain longer than in some of the other CMR-affected breeds. In rare severe cases, the clinical diagnosis could be confused with progressive retinal atrophy (PRA). The full range of clinical symptoms will learned as more dogs are tested for their genetic status.
The clinical presentation and pathology of CMR closely resembles lesions of “Best vitelliform dystrophy”, a human disease with variable clinical expression but usually with serious affects on central vision. Identification of the gene mutation responsible for CMR was based on these similarities. A mutation in the human VMD2 gene – Vitelliform Macular Dystrophy 2 Gene – causes dominantly inherited human Best Disease. Analysis of the canine version of the VMD2 gene indicates that mutations in it cause CMR as a recessively inherited canine condition. The normal form of the VMD2 gene produces a protein named “bestrophin”. The bestrophin protein assembles, in the cells of the retinal pigment epithelium, in
a group of four or five units that form a pore through which chloride ions pass.
Our current understanding is that CMR is inherited in an autosomal recessive pattern. This means the gene mutation responsible for CMR is located on an autosome (that is, a chromosome that is not a sex chromosome) and CMR disease results when the gene mutation is passed to the offspring by both the mother and the father. It should be noted that the human disease that mirrors CMR in dogs is an autosomal dominant disease with incomplete penetrance. This means that sometimes, but not always, only one copy of the disease gene needs to be present in order for the disease to be observed clinically. At this point CMR in dogs is NOT considered to be an autosomal dominant disease however as more animals are characterized genetically with the CMR test, it is possible that we will find a similar form of inheritance as is seen in humans.
There is complete concordance of the mutation with the disease among affected dogs in the Mastiffs, Great Pyrenees, Australian Shepherds, Coton de Tulear and Lapponian Herders. However, retinal dysplasia described in other breeds, for example in Labradors, Samoyeds or English Springer Spaniels, is very distinct in comparison to CMR and these conditions are not caused by the CMR mutation. Due to the abnormal appearance of the CMR-affected retina, CERF, ACVO, ECVO and other ophthalmologist’s eye exam reports typically record these multi-focal lesions as “retinal dysplasia” or “retinal folds”, to denote a defect in formation of the retina. Such findings might disqualify the dog from breeding. Presently CERF
doesn’t list CMR as a specific condition, but does fail a dog for “retinal dysplasia/retinopathy – folds, detached.”
The genetic test for CMR is valuable for identifying the cause of a retinal deformation. Given the exact genetic diagnosis, the owner can be reassured that there probably will be little or no vision loss due to this condition. All the same, future cases of the condition can be prevented using the CMR test as an information tool for breeding Genetic Testing:
An exact diagnosis of this eye condition can be difficult. Definitive clinical diagnosis might even change due to the changing appearance of the retina as the dog ages. The CMR genetic test solves this problem immediately since presence of the CMR gene mutation is detected by testing a DNA sample. This result gives the owner immediate diagnostic information and aides in making decisions for the affected dog and for breeding strategies.
Degenerative Myelopathy (DM)
Degenerative myelopathy is an inherited neurologic disorder caused by a Mutation of the SOD1 gene known to be carried by Miniature Australian Shepherds. This mutation is found in many breeds of dog, though it is not clear for Miniature Australian Shepherds whether all dogs carrying two copies of the mutation will develop the disease. The variable presentation between breeds suggests that there are environmental or other genetic factors responsible for modifying disease expression. The average age of onset for dogs with degenerative myelopathy is approximately nine years of age. Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog, but will progress until the dog is no longer able to walk. The gait of dogs affected with degenerative myelopathy can be difficult to distinguish from the gait of dogs with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of disease, dogs may lose fecal and urinary continence and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of symptoms. Affected small breed dogs, such as Miniature Australian Shepherds, often progress more slowly than affected large breed dogs and owners may postpone euthanasia until the dog is paraplegic.
Breed-Specific Information for the Miniature Australian Shepherd The Mutation of the SOD1 gene associated with degenerative myelopathy has been identified in Miniature Australian Shepherds in the Paw Print Genetics laboratory. The frequency of the causal mutation has not been reported in the medical literature for the Miniature Australian Shepherds. It is unknown for this breed if dogs carrying two copies of this mutation develop the clinical signs of degenerative myelopathy.
Testing Tips Genetic testing of the SOD1 gene in Miniature Australian Shepherds will reliably determine whether a dog is a genetic Carrier of degenerative myelopathy. Degenerative myelopathy is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the SOD1 gene mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood and some at-risk/affected dogs do not develop the disease, genetic testing should be performed before breeding. Until the exact modifying environmental or genetic factor is determined, genetic testing remains the only reliable way to detect neurological disease associated with this mutation prior to death. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Miniature Australian Shepherds that are not carriers of the mutation have no increased risk of having affected pups.
Breed-Specific Information for the Miniature Australian Shepherd The Mutation of the SOD1 gene associated with degenerative myelopathy has been identified in Miniature Australian Shepherds in the Paw Print Genetics laboratory. The frequency of the causal mutation has not been reported in the medical literature for the Miniature Australian Shepherds. It is unknown for this breed if dogs carrying two copies of this mutation develop the clinical signs of degenerative myelopathy.
Testing Tips Genetic testing of the SOD1 gene in Miniature Australian Shepherds will reliably determine whether a dog is a genetic Carrier of degenerative myelopathy. Degenerative myelopathy is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the SOD1 gene mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood and some at-risk/affected dogs do not develop the disease, genetic testing should be performed before breeding. Until the exact modifying environmental or genetic factor is determined, genetic testing remains the only reliable way to detect neurological disease associated with this mutation prior to death. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Miniature Australian Shepherds that are not carriers of the mutation have no increased risk of having affected pups.
