Genetics of inherited skin disorders in dogs

Leeb, Tosso; Roosje, Petra; Welle, Monika Maria

doi:10.1016/j.tvjl.2021.105782

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…Whole genome sequencing, with the ability to identify the underlying genetic defect of inherited diseases, has become more accessible in veterinary medicine (Leeb, Bannasch, et al, 2022a). Together with clinical and histopathological examinations, genetic investigations offer a unique opportunity for a relatively fast and low‐invasivity precise diagnosis, which in turn enables a more accurate prognosis and potentially even targeted therapy (Leeb, Roosje, et al, 2022b; Park et al, 2022). The objective of this study was to clinically and histopathologically characterize a cornification disorder in a Chihuahua and to investigate a possible underlying genetic defect.…”

Section: Figurementioning

confidence: 99%

SDR9C7 missense variant in a Chihuahua with non‐epidermolytic ichthyosis

Kiener

Castilla²,

Jagannathan

et al. 2023

Animal Genetics

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Ichthyoses represent a heterogeneous group of cornification disorders that are associated with skin barrier defects. We investigated a 9-monthold Chihuahua showing excessive scale formation. Clinical and histopathological examinations revealed non-epidermolytic ichthyosis and a genetic defect was suspected. We therefore sequenced the genome of the affected dog and compared the data with 564 genetically diverse control genomes. Filtering for private variants identified a homozygous missense variant in SDR9C7, c.454C>T or p.(Arg152Trp). SDR9C7 is a known candidate gene for ichthyosis in humans and encodes the short-chain dehydrogenase/ reductase family 9C member 7. The enzyme is involved in the production of a functional corneocyte lipid envelope (CLE), a crucial component of the epidermal barrier. Pathogenic variants in SDR9C7 have been described in human patients with autosomal recessive ichthyosis. We assume that the identified missense variant in the affected Chihuahua of this study impairs the normal enzymatic activity of SDR9C7 and thus prevents the formation of a functioning CLE, resulting in a defective skin barrier. To the best of our knowledge, this is the first report of a spontaneous SDR9C7 variant in domestic animals.

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Section: Figurementioning

confidence: 99%

SDR9C7 missense variant in a Chihuahua with non‐epidermolytic ichthyosis

Kiener

Castilla²,

Jagannathan

et al. 2023

Animal Genetics

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“…While cases of KRT1 -related ichthyosis have been documented in humans, they have not been reported in dogs to date [ 12 – 14 ]. This investigation documents a congenital cornification disorder in a Chinese shar-pei puppy due to a 3 base pair deletion in the KRT1 gene.…”

Section: Introductionmentioning

confidence: 99%

A de novo variant in the keratin 1 gene (KRT1) in a Chinese shar-pei dog with severe congenital cornification disorder and non-epidermolytic ichthyosis

Affolter

Kiener²,

Jagannathan³

et al. 2022

PLoS ONE

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A 3-months old Chinese shar-pei puppy with ichthyosis was investigated. The dog showed generalized scaling, alopecia and footpad lesions. Histopathological examinations demonstrated a non-epidermolytic hyperkeratosis. The parents of the affected puppy did not show any skin lesions. A trio whole genome sequencing analysis identified a heterozygous de novo 3 bp deletion in the KRT1 gene in the affected dog. This variant, NM_001003392.1:c.567_569del, is predicted to delete a single asparagine from the conserved coil 1A motif within the rod domain of KRT1, NP_001003392.1:p.(Asn190del). Immunohistochemistry demonstrated normal levels of KRT1 expression in the epidermis and follicular epithelia. This might indicate that the variant possibly interferes with keratin dimerization or another function of KRT1. Missense variants affecting the homologous asparagine residue of the human KRT1 cause epidermolytic hyperkeratosis. Histologically, the investigated Chinese shar-pei showed a non-epidermolytic ichthyosis. The finding of a de novo variant in an excellent functional candidate gene strongly suggests that KRT1:p.Asn190del caused the ichthyosis phenotype in the affected Chinese shar-pei. To the best of our knowledge, this is the first description of a KRT1-related non-epidermolytic ichthyosis in domestic animals.

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“…The identification of a pathogenic variant and thus the molecular characterization of a suspected inherited disease is of great value as it provides a fast and minimally invasive definitive diagnosis. Further, it offers the opportunity to give breeding recommendations and may even provide guidance for targeted therapy (Leeb et al, 2022 ). Therefore, the aim of this study was to characterize the clinical and histopathological phenotype of the affected puppy and to identify the underlying genetic variant using a whole genome sequencing approach.…”

Section: Introductionmentioning

confidence: 99%

KRT5 missense variant in a Cardigan Welsh Corgi with epidermolysis bullosa simplex

et al. 2022

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Epidermolysis bullosa (EB) comprises a heterogeneous group of blistering disorders. They are characterized by blisters and erosions resulting from minimal trauma (Fine et al., 2008;Has et al., 2018). Classification into different types of EB is based on the level of cleavage. These are EB simplex (EBS), with a level of cleavage in the basal layer of the epidermis, junctional EB, with a level of cleavage at the dermo-epidermal junction, and dystrophic EB, with a level of cleavage just below the basal membrane. The fourth category, Kindler EB, with a mixed level of cleavage, is a rare EB type with a very severe clinical phenotype (Has et al., 2020). The human classification is also the basis for the classification of EB types in animals (Medeiros & Riet-Correa, 2015).

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Genetics of inherited skin disorders in dogs

Cited by 5 publications

References 58 publications

SDR9C7 missense variant in a Chihuahua with non‐epidermolytic ichthyosis

SDR9C7 missense variant in a Chihuahua with non‐epidermolytic ichthyosis

A de novo variant in the keratin 1 gene (KRT1) in a Chinese shar-pei dog with severe congenital cornification disorder and non-epidermolytic ichthyosis

KRT5 missense variant in a Cardigan Welsh Corgi with epidermolysis bullosa simplex

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