ABHD5 frameshift deletion in Golden Retrievers with ichthyosis

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 non-epidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 non-affected 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 co-segregation 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).

Dry skin disorders

This chapter on dry skin disorders describes a range of mainly genetic dermatoses whose predominant feature is dry scaly skin. It excludes conditions such as eczema where dry skin is a secondary clinical sign. The underlying mechanism of dry scaly skin is briefly discussed and an algorithm points to possible diagnoses. The focus is on the genetic ichthyoses, defined as congenital, lifelong, generalized dry and scaly skin. The common ichthyoses are non-inflammatory (ichthyosis vulgaris and X-linked recessive ichthyosis) but there are several inflammatory ichthyoses, some associated with fragile skin (blistering) and several with multisystem complications, such as Netherton syndrome. Salient features of each are reviewed with illustrations of selected cases and management is outlined. Two important neonatal presentations, collodion baby and harlequin ichthyosis, are described.