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Second form of non-epidermolytic ichthyosis in the Golden Retriever, described in 2022 and caused by a 14-base-pair deletion in exon 7 of the ABHD5 gene (α/β-hydrolase domain-containing 5, formerly CGI-58). ABHD5 is an acyltransferase required for epidermal lipid metabolism and the biosynthesis of the ω-O acylceramides that form the skin barrier. Clinically it resembles ichthyosis type 1 (PNPLA1), although breeders describe more severe and adherent scales. It is autosomal recessive and, to date, appears restricted to North American lines of the breed.

Affected breed: Golden Retriever, especially North American lines. The variant has not been found in 396 tested Golden Retrievers of European origin (Kiener et al. 2022, PMID 34791225). To date, published cases are scarce and the frequency appears low outside North America; consider "limited data" for reliable allele frequencies.

- Generalised whitish or blackish scales from the first weeks of life\n- Larger, lamellar and adherent scales than in ICH1, according to breeders\n- Coat with a dishevelled appearance\n- Orthokeratotic laminated/compact hyperkeratosis with hypergranulosis and mild acanthosis on histology\n- No marked inflammatory erythema\n- Heterozygous dogs clinically normal

After the identification in 2012 of PNPLA1 as the gene for ichthyosis type 1 in the Golden Retriever, it was observed that some Golden Retrievers with typical clinical and histological ichthyosis were not homozygous for the PNPLA1 variant. Kiener and colleagues investigated in 2022 a family of 14 cases and 72 controls with an ichthyosis phenotype not explained by PNPLA1. Whole-genome resequencing of one affected dog, compared with 795 control genomes, identified a single homozygous coding variant in the mapped critical region: a 14-bp deletion in ABHD5 (c.1006_1019del, p.Asp336Serfs*6) that alters the last 14 codons of the α/β-hydrolase domain, including part of the codons essential for the catalytic function of the protein. The variant segregated perfectly in the 14 cases. The phenotypic parallelism with human ABHD5-related ichthyosis and the available functional data support causality. The authors proposed naming this form Golden retriever ichthyosis type 2 (ICH2).

- Test Golden Retriever breeding animals with the ABHD5 c.1006_1019del test before mating, especially in lines of North American ancestry\n- Ideally, combine with the PNPLA1 test in an ICH1+ICH2 panel so that no carrier is missed\n- Do not mate two ABHD5 carriers: 25 % risk of affected homozygotes in each litter\n- A carrier may be mated to a clear animal; the offspring intended for breeding should be tested and clear animals preferably selected\n- Exclude affected homozygous animals from breeding\n- In Golden Retrievers with generalised scales without the PNPLA1 variant, suspect ICH2 and confirm with the ABHD5 test before any mating of the parents\n- Communicate the status to the buyer and record the result in the pedigree

Differential diagnosis with ichthyosis type 1 due to PNPLA1 (clinically indistinguishable; only molecular testing separates them) and with the other canine ichthyoses (SLC27A4 in the Great Dane, NIPAL4 in the American Bulldog, KRT10 in the Norfolk Terrier, TGM1 in the Jack Russell Terrier), atopic dermatitis and primary seborrhoea. Biopsy does not distinguish ICH1 from ICH2; molecular testing is decisive. Management is palliative: emollients, keratolytic baths (salicylic acid, urea), control of secondary infections. Since ICH1 carriers may also be ICH2 carriers (or vice versa), the combined panel is the safest option in North American lines.

1. Kiener S, Wiener DJ, Hopke K, Diesel AB, Jagannathan V, Mauldin EA, Casal ML, Leeb T. (2022) ABHD5 frameshift deletion in Golden Retrievers with ichthyosis. G3 (Bethesda) 12:jkab397. PMID: 34791225
2. Grall A, Guaguère E, Planchais S, et al. (2012) PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans. Nat Genet 44:140-147. PMID: 22246504
3. De Iorio MG, et al. (2026) Prevalence and genotypic distribution of non-epidermolytic ichthyosis in Italian Golden Retrievers. PLoS One 21:e0345595. PMID: 41875098