ABHD5 frameshift deletion in Golden Retrievers with ichthyosis

G3 (Bethesda). 2022 Feb 4;12(2):jkab397. doi: 10.1093/g3journal/jkab397.


Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 nonaffected family members delimited a critical interval of ∼12.7 Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14 bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2).

Keywords: Canis lupus familiaris; animal model; dermatology; dog; genodermatosis; lipid storage disorder; metabolism; precision medicine; veterinary medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Acylglycerol-3-Phosphate O-Acyltransferase* / genetics
  • Animals
  • Dogs
  • Frameshift Mutation
  • Gene Deletion
  • Ichthyosiform Erythroderma, Congenital* / genetics
  • Ichthyosiform Erythroderma, Congenital* / pathology
  • Ichthyosis* / genetics
  • Ichthyosis* / pathology
  • Ichthyosis* / veterinary
  • Ichthyosis, Lamellar* / genetics
  • Ichthyosis, Lamellar* / veterinary
  • Lipid Metabolism, Inborn Errors* / genetics
  • Lipid Metabolism, Inborn Errors* / pathology
  • Plant Breeding


  • 1-Acylglycerol-3-Phosphate O-Acyltransferase