Ichthyosis 1 in Golden Retriever

Ichthyosis is a heterogeneous group of genodermatoses characterized by abnormal scaling of skin over the whole body. The word ichthyosis comes from the Greek ichthys, meaning fish, as the scaling skin resembles the scales on a fish. The genetic causes of some forms of ichthyosis remain unknown.

In Golden Retrievers, a lamellar form of ichthyosis 1 was described. In all affected dogs, an insertion-deletion mutation in exon 8 of  PNPLA1-gene (patatin-like phospholipase domain-containing protein 1) was identified that leads to a premature stop codon (Grall et al. 2012). In dogs, the PNPLA1gene was localized on the chromosome CFA12. Golden Retrievers represent an animal model resembling the human autosomal recessive congenital ichthyosis (ARCI - autosomal recesive congenital ichtyosis).  The knowledge gained from clarification of ichthyosis cause  in Golden Retrievers was used in human patients affected with ichthyosis. In non-relative patients, mutations in the catalytic domain of  PLPLA1 gene were identified, which have not caused any human disease so far (Grall et al. 2012). PNPLA1 is apparently involved in formation of the epidermal lipid barrier.

Genetic causes of ichthyosis were also proven  in other dog breeds. In Jack Russel Terrier breed, an insertion of LINE-1 element in TGM1-gene (transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase), located on the chromosome CFA8, was identified in connection with the ichthyosis (Credille et al. 2009). In this case, the protective function of the skin is destroyed due to transglutaminase defect. In affected dogs of Norfolk Terrier breed, a mutation in KRT10 gene localized on the canine chromozome 9 was identified (Credille et al. 2005).

The Genomia laboratory examinates the presence of insertion-deletion mutation in exon 8 of PNPLA1 gene (patatin-like phospholipase domain-containing protein 1) that causes Ichthyosis 1 in Golden Retriever breed. We also offer a test for Ichthyosis 2, which is caused by a 14 bp deletion in the ABHD5 gene. The frequency of this mutation in the population is lower than the frequency of the mutation causing ichthyosis 1.

In puppies of Golden Retrievers affected by ichthyosis, skin scaling is eveident soon after birth. The skin scaling lasts through the whole life of the animal. The scales become dark and the skin dry and rough with the age of the animal.  This disease does not usually cause itching. In severely affected animals, the disease can be complicated by secondary bacterial, fungal or parasitic infectons.

Currently,  there is no effective treatment available. The treatment usually relies in increased hygiene measures with frequent brushing, application of special shampoos, softening oitments and food reach in fatty acids.

The ichthyosis 1 is not a new disease, it has been observed in many Retrievers worldwide for a long time, however it was not published before 2012 (Grall et al. 2012).

Ichthyosis 1 in Golden Retriever is inherited as an autosomal recessive trait. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive /negative) genotype are clinically without any symptom. They are genetically 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.  Both types of mutant alleles (ICTA1 and ICTA2) can occur simultaneously in dogs. However, individuals with N/P genotypes for both mutations are still asymptomatic.

.

References: