Intragenic PNPLA1 duplication in Labrador retrievers with nonepidermolytic ichthyosis

BACKGROUND: Ichthyoses represent a heterogeneous group of cornification disorders characterised by epidermal scaling. OBJECTIVES: To describe the clinical, histopathological and genetic analysis of a Labrador retriever with nonepidermolytic ichthyosis, and the results of a population screening for a newly detected PNPLA1 genomic duplication. ANIMALS: Two 7-year-old male littermates, 531 population samples. MATERIALS AND METHODS: Clinical and histopathological analysis, whole genome sequencing and digital PCR-based genotyping were performed. RESULTS: Generalised scaling and histological laminar orthokeratotic hyperkeratosis confirmed the ichthyosis diagnosis on Dog 1. Dog 2 showed mild clinical signs possibly associated with allergies and not ichthyosis. The genome of Dog 1 was sequenced and compared to 1469 genetically diverse control genomes. The analysis identified a 6099-bp duplication spanning three internal exons of the PNPLA1 gene, which is predicted to result in an altered C-terminal tail of the protein, NP_001277038.2:p.(E558Lfs*17). Dog 2 had a heterozygous genotype and carried one copy of the duplicated PNPLA1 allele. Of the screened 531 additional Labrador retrievers, 491 were homozygous wild-type, 36 were heterozygous carriers and four carried the duplication in a homozygous state. CONCLUSIONS AND CLINICAL RELEVANCE: Previously identified PNPLA1 variants cause autosomal recessive ichthyosis in golden retrievers and humans. Given the well-established function of PNPLA1, the identified genomic duplication represents a likely candidate causal variant for the observed ichthyosis in the examined Labrador retriever. This is the first report of a new form of autosomal recessive ichthyosis in Labrador retrievers, which provides the basis for genetic testing.

Authors: S. J. Rietmann, J. L. Clegg, V. Jagannathan, D. J. Wiener, A. Kallenberg, R. A. Grahn, C. P. Souza and T. Leeb Title: Intragenic PNPLA1 duplication in Labrador retrievers with nonepidermolytic ichthyosis Full source: Vet Dermatol, 2025,Vol Document type: Journal Article
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Abstract	Source
BACKGROUND: Ichthyoses represent a heterogeneous group of cornification disorders characterised by epidermal scaling. OBJECTIVES: To describe the clinical, histopathological and genetic analysis of a Labrador retriever with nonepidermolytic ichthyosis, and the results of a population screening for a newly detected PNPLA1 genomic duplication. ANIMALS: Two 7-year-old male littermates, 531 population samples. MATERIALS AND METHODS: Clinical and histopathological analysis, whole genome sequencing and digital PCR-based genotyping were performed. RESULTS: Generalised scaling and histological laminar orthokeratotic hyperkeratosis confirmed the ichthyosis diagnosis on Dog 1. Dog 2 showed mild clinical signs possibly associated with allergies and not ichthyosis. The genome of Dog 1 was sequenced and compared to 1469 genetically diverse control genomes. The analysis identified a 6099-bp duplication spanning three internal exons of the PNPLA1 gene, which is predicted to result in an altered C-terminal tail of the protein, NP_001277038.2:p.(E558Lfs*17). Dog 2 had a heterozygous genotype and carried one copy of the duplicated PNPLA1 allele. Of the screened 531 additional Labrador retrievers, 491 were homozygous wild-type, 36 were heterozygous carriers and four carried the duplication in a homozygous state. CONCLUSIONS AND CLINICAL RELEVANCE: Previously identified PNPLA1 variants cause autosomal recessive ichthyosis in golden retrievers and humans. Given the well-established function of PNPLA1, the identified genomic duplication represents a likely candidate causal variant for the observed ichthyosis in the examined Labrador retriever. This is the first report of a new form of autosomal recessive ichthyosis in Labrador retrievers, which provides the basis for genetic testing.