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Nasal parakeratosis (SUV39H2 gene, Labrador Retriever)

Nasal parakeratosis (SUV39H2 gene, Labrador Retriever)

The epidermis is the outermost layer of the skin and is continually renewed throughout life by the constant proliferation of keratinocytes, the specialized cells that make up the epidermis. Nasal parakeratosis is an autosomal recessive disorder that arises due to a defect in this process of cell differentiation in the epidermis, manifesting mainly in the early appearance of crusts and fissures on the nasal plane (upper edge of the nose).

Symptoms

Nasal parakeratosis presents clinically with non-pruritic hyperkeratosis on the nasal plane, showing obvious clinical signs between 6 and 24 months of age. Symptoms vary from mild lesions, such as hyperkeratosis of the dorsal nasal plane, to more severe cases with fissures and erosions. Hyperkeratosis involves an abnormal increase in keratin and, in the case of nasal parakeratosis, is characterized by the accumulation of protein fluid ("serum lakes") in the stratum corneum, retention of nuclei in this stratum of the epidermis, and the presence of variable inflammation in the dermis and epidermis. Despite these cutaneous symptoms, affected dogs remain generally healthy.

Disease Management

Management of nasal parakeratosis includes the application of topical moisturizers to maintain skin hydration and reduce excessive keratin accumulation on the nasal plane. In more severe cases with fissures or erosions, specific treatments are employed to promote healing and prevent infection. Immunomodulatory options, such as topical corticosteroids or tacrolimus, may be considered to reduce inflammation. Monitoring and treating secondary infections is crucial, and regular veterinary follow-up allows the treatment plan to be adjusted as needed.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Nasal parakeratosis has been linked to two distinct variants, each present in two specific breeds: Labrador Retriever and English Greyhound. In both cases, the associated gene is SUV39H2, responsible for encoding a histone modifying enzyme. The function of SUV39H2 is based on catalyzing the addition of methyl groups to the lysine 9 residue of histone 3 (H3K9), thus modulating chromatin structure and causing transcriptional silencing. This phenomenon prevents the expression of the affected gene, resulting in the absence of the corresponding protein. Notably, lysine methylation in non-histone proteins also plays a regulatory role in signal transduction pathways crucial for epidermal differentiation, such as MAPK, WNT and JAK-STAT. In our study, we analyzed the variant described in the Labrador Retriever breed (c.972T>G). This is a nonsense variant affecting a highly conserved amino acid residue of the SET domain, and is therefore estimated to completely or almost completely suppress the methyltransferase function of SUV39H2.

Most affected breeds

Labrador Retriever
English Greyhound

Bibliography

Bannoehr J, Balmer P, Stoffel MH, et al. Abnormal keratinocyte differentiation in the nasal planum of Labrador Retrievers with hereditary nasal parakeratosis (HNPK). PLoS One. 2020 Mar 2;15(3):e0225901.

Jagannathan V, Bannoehr J, Plattet P, et al. A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation. PLoS Genet. 2013;9(10):e1003848.

Pagé N, Paradis M, Lapointe JM, et al. Hereditary nasal parakeratosis in Labrador Retrievers. Vet Dermatol. 2003 Apr;14(2):103-10.