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.
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, Ich = congenital ichthyosis variant
Breeds appropriate for testing: Golden Retriever and Golden Retriever crosses
Explanation of Results:
Dogs with N/N genotype do not have the variant associated with ichthyosis found in Golden Retrievers.
Dogs with N/Ich genotype 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 Ich/Ich genotype are homozygous for the ichthyosis variant found in Golden Retrievers and are expected to develop ichthyosis, although the presentation may be variable.
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 become 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.
Congenital ichthyosis in the Golden Retriever is inherited in an autosomal recessive fashion. Two copies of the variant must be present for the disease to manifest, and both sexes are equally affected.
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 Ich/Ich should be clinically evaluated.
Note: This test is specific for the autosomal recessive PNPLA1 variant present in the Golden Retriever. This assay does not detect the ichthyoses variants in other breeds.
Normal. Dog does not have the variant associated with congenital ichthyosis found in Golden Retrievers.
Carrier. Dog has one copy of the variant associated with congenital ichthyosis found in Golden Retrievers.
Affected. Dog has two copies of the variant associated with ichthyosis found in Golden Retrievers and will likely develop the disease.
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