ABHD5 frameshift deletion in Golden Retrievers with ichthyosis.

Kiener, Sarah; Wiener, Dominique J; Hopke, Kaitlin; Diesel, Alison B; Jagannathan, Vidhya; Mauldin, Elizabeth A; Casal, Margret L; Leeb, Tosso (2022). ABHD5 frameshift deletion in Golden Retrievers with ichthyosis. G3 Genes Genomes Genetics, 12(2) Genetics Society of America 10.1093/g3journal/jkab397

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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).

Item Type:

Journal Article (Original Article)


09 Interdisciplinary Units > Next Generation Sequencing (NGS) Platform
05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kiener, Sarah, Jagannathan, Vidya, Leeb, Tosso


500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health




Genetics Society of America




Tosso Leeb

Date Deposited:

01 Apr 2022 15:07

Last Modified:

05 Dec 2022 16:17

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Canis lupus familiaris animal model dermatology dog genodermatosis lipid storage disorder metabolism precision medicine veterinary medicine





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