Congenital Ichthyosis 1 and 2 in Golden Retrievers

Quick Summary

Congenital ichthyosis is a skin condition in which the outer layer of the skin does not form properly and results in scaling. The condition often progresses to large patches of thickened, black, scaly skin. Two genetic variants have been associated with congenital ichthyosis in the Golden Retriever.

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Phenotype: A skin condition that results in a mild to moderate and in some cases severe scaling of the skin, usually excluding the head, extremities, paw pads, and nose. Scales become pigmented, progressing to gray or black, and range in size from small to large. These scales may give the dog’s hair and skin a “dirty” look as the scales progress to a darker color.

Mode of Inheritance: Autosomal recessive

Alleles: N = Normal, Ich1* = congenital ichthyosis 1 variant, Ich2 = congenital ichthyosis 2 variant 

Breeds appropriate for testing: Golden Retriever

Explanation of results:
•    Dogs with N/N genotype do not have either of the known Ichthyosis variants
•    Dogs with N/Ich1 or N/Ich2 genotypes are carriers of the ichthyosis variant found in Golden Retrievers but will not develop ichthyosis. If two carriers are mated, approximately 25% of the puppies are predicted to develop disease and 50% are predicted to be carriers.
•    Dogs with Ich1/Ich1 or Ich2/Ich2 genotype are homozygous for the ichthyosis variants found in Golden Retrievers and are expected to develop ichthyosis, although the presentation may be variable.

*Note: The Ich1 allele was previously reported by the VGL as Ich

Results of this test can be submitted to the OFA (Orthopedic Foundation for Animals)

Price

$50 single test per animal ($5 discount on 3 or more dogs)
$30 as additional test on same animal

Note: ICH1 and ICH2 are two separate tests. To test for both variants, please make sure to select both tests on the order form. The price for both ICH1 and ICH2 is $80. Alternatively, both ICH1 and ICH2 are included in the Golden Retriever Health Panel.
Panels Available
Turnaround Time
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
Additional Details

Ichthyoses are a group of genetic skin disorders characterized by defects in the formation of the stratum corneum (the outer layer of the epidermis) that result in scaling of the skin and desquamation (shedding of the outer layer of the skin, or more colloquially, skin peeling). In the Golden Retriever, symptoms of a breed-specific ichthyosis include mild to moderate, and in some cases severe, generalized scaling on the body, usually excluding the head, extremities, paw pads, and nose. The scales are initially a whitish color but becomes pigmented, progressing to gray or black, and they range in size from small to large. These scales may give the dog’s hair and skin a “dirty” look, especially as the pigmented scales shed and adhere to the coat. Age of onset is generally early: clinical signs have been detected as early as 3-6 weeks of age in some dogs, although in others, the signs may not become readily apparent until months or even years later. Early symptoms of the disease may go unnoticed by owners due in part to their subtly and the less severe symptoms noted in the Golden Retriever when compared to other dog breeds.

In humans, over 30 different genes that result in various ichthyoses have been identified. In dogs, at least 12 different breed-specific types of ichthyosis have been described, but genetic mechanisms have only been identified in a few breeds. An insertion-deletion variant (often referred to as an indel) in the patatin-like phospholipase domain-containing protein 1 (PNPLA1) gene was identified as perfectly correlated with the congenital ichthyosis disease in Golden Retrievers. In total, 360 Golden Retrievers were evaluated in the initial study and this variant was perfectly concordant with disease status, providing evidence that this variant is responsible for disease. Additionally, this variant was absent in 300 healthy dogs from 25 other breeds.

It is predicted that this variant (also denoted as c.1445_1447delinsTACTACTA) causes a frameshift in the protein product, which would produce a premature stop codon (p.N482Ifs*11), and thus the altered protein product is predicted to be shorter than the normal product. Though the exact consequences of this protein truncation are currently unknown, it is hypothesized that this defective PNPLA1 protein causes lipid defects and does not allow the proper formation of keratinocytes (the cells in the epidermis that produce keratin) in the outermost layer of skin.

Some Golden Retrievers with ichthyosis, however, do not have the PNPLA1 variant. A study published in 2022 looked at 14 Golden Retrievers diagnosed with congenital ichthyosis that did not have the PNPLA1 variant and identified a second genetic variant strongly associated with congenital ichthyosis in the breed. The variant identified in the ABHD5 gene consists of a 14 bp deletion (denoted as c.1006_1019del) that also causes a frameshift and premature stop codon in the resulting protein (pD336Sfs*6). The study showed that the variant was only present in North American Golden Retrievers, being absent in over 390 Golden Retrievers of European origin.

Researchers proposed that congenital ichthyosis caused by the PNPLA1 variant be referred to as congenital ichthyosis type 1 (ICH1) and that caused by the ABHD5 variant be called congenital ichthyosis type 2 (ICH2). The clinical and histological presentation of ICH2 is similar to that seen with ICH1, although the researchers noted that breeders reported more severe and adherent scaling with ICH2.

Both types of congenital ichthyosis in the Golden Retriever are inherited in an autosomal recessive fashion. Two copies of either variant must be present for the disease to manifest, and both sexes are equally affected. Testing recommendations: In the initial study that identified the causal genetic variant, researchers reported the variant occurred at high frequency in the breed (50%). Testing for this variant can assist veterinarians with diagnosis and helps breeders identify carriers among breeding stock to select appropriate mates that will reduce the risk of producing affected offspring. To avoid the possibility of producing affected puppies, matings between known carriers is not recommended. However, with the reportedly high frequency, it is advisable to select away from this mutation over several generations to assist in maintaining diversity. Dogs who genotype as Ich1/Ich1 or Ich2/Ich2 should be clinically evaluated.

 

Note: This test is specific for the autosomal recessive variants present in the Golden Retriever: the PNPLA1 variant (Ich1) and the ABHD5 variant (Ich2). This assay does not detect the ichthyoses variants found in other breeds

Species

Dog

Type of Test

Results Reported As
Test Result Congenital Ichthyosis 1 (Ich1)

N/N

Normal. Dog does not have the variant associated with congenital ichthyosis 1 found in Golden Retrievers.

N/Ich1

Carrier. Dog has one copy of the variant associated with congenital ichthyosis 1 found in Golden Retrievers.

Ich1/Ich1

Affected. Dog has two copies of the variant associated with congenital ichthyosis 1 found in Golden Retrievers and will likely develop the disease.

 

Test Result Congenital Ichthyosis 2 (Ich2)

N/N

Normal. Dog does not have the variant associated with congenital ichthyosis 2 found in Golden Retrievers.

N/Ich2

Carrier. Dog has one copy of the variant associated with congenital ichthyosis 2 found in Golden Retrievers.

Ich2/Ich2

Affected. Dog has two copies of the variant associated with congenital ichthyosis 2 found in Golden Retrievers and will likely develop the disease.

References

Grall, A., Guaguère, E., Planchais, S., Grond, S., Bourrat, E., Hausser, I., Hitte, C., Le Gallo, M., Derbois, C., Kim, G.J., Lagoutte, L., Degorce-Rubiales, F., Radner, F.P., Thomas, A., Küry, S., Bensignor, E., Fontaine, J., Pin, D., Zimmermann, R., Zechner, R., Lathrop, M., Galibert, F., André, C., & Fischer, J. (2012). PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nature Genetics, 44(2), 140-147. doi: 10.1038/ng.1056

Kiener, S., Wiener, D. J., Hopke, K., Diesel, A. B., Jagannathan, V., Mauldin, E. A., Casal, M. L., & Leeb, T. (2022). ABHD5 frameshift deletion in Golden Retrievers with ichthyosis. G3 (Bethesda, Md.), 12(2), jkab397. https://doi.org/10.1093/g3journal/jkab397