OMIA 001373-9615 : Nasal parakeratosis in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 606503

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Species-specific name: Hereditary nasal parakeratosis

Species-specific symbol: HNPK

Inheritance: Page et al. (2003) reported evidence consistent with autosomal recessive inheritance.

Mapping: A GWAS conducted by Jagannathan et al. (2013) on 13 affected and 23 control Labrador retrievers, each genotyped with the Illumina canine HD chip (yielding 106,681 informative SNPs), mapped this disorder to an approximately 4Mb region on chromosome CFA2. Subsequest homozygosity mapping narrowed the candidate region to approximately 1.6Mb "from 20,818,258–22,414,948 bp (CanFam 3.1 assembly)" which contains 15 annotated genes.

Molecular basis: Whole-genome sequencing of one of the affected dogs by Jagannathan et al. (2013), and comparison of this sequence in the ~1.6Mb candidate region with the canine reference sequence revealed four non-synonymous variants, one of which "turned out to represent an artifact due to an error in the reference genome assembly". Genotyping of the other three variants in a large (>500) cohort of affected and control dogs identifed the causal mutation as c.972T>G in the SUV39H2 gene "encoding the “suppressor of variegation 3-9 homolog 2 (Drosophila)”, a histone 3 lysine 9 (H3K9) methyltransferase". "The variant results in the change of an asparagine residue in the catalytically active SET domain to a lysine (p.N324K). The SET domain has been named according to the first proteins, in which it has been identified, Suvar(3)9, enhancer of zeste, and trithorax. SIFT and Polyphen-2 predict that the p.N324K variant affects protein function . . . . The asparagine at position 324 is highly conserved across all known SUV39H2 orthologs and even across many other related H3K9 methyltransferases". The same authors also comment that "A loss of SUV39H2 function is predicted to result in delayed differentiation, which is compatible with the histopathological changes that we observed in biopsies from nasal epidermis of HNPK affected Labrador Retrievers."

Bauer et al. (2018): "Whole genome sequencing of one affected Greyhound revealed a 4-bp deletion at the 5′-end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5′-splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non-affected littermates were heterozygous."

Clinical features: As summarised by Jagannathan et al. (2013), "HNPK affected dogs develop crusts and fissuring of the nasal planum at a young age but are otherwise healthy. The pathognomonic histopathological changes consist of a marked diffuse parakeratotic hyperkeratosis characterized by the retention of nuclei in the stratum corneum and an accumulation of proteinaceous fluid (“serum lakes”) within the stratum corneum".

Breeds: Greyhound, Labrador Retriever.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SUV39H2 suppressor of variegation 3-9 homolog 2 (Drosophila) Canis lupus familiaris 2 NC_006584.3 (21749732..21715677) SUV39H2 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the required column headers

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Greyhound Nasal parakeratosis SUV39H2 deletion, small (<=20) CanFam 3.1 2 g.21731812_21731815delACTT c.996+3_996+6delAAGT 2018 29423952
Labrador Retriever Nasal parakeratosis SUV39H2 missense CanFam3.1 2 g.21731842A>C c.972T>G p.N324K 2013 24098150

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Bauer, A., Nimmo, J., Newman, R., Brunner, M., Welle, M.M., Jagannathan, V., Leeb, T. :
A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis. Anim Genet 49:137-140, 2018. Pubmed reference: 29423952. DOI: 10.1111/age.12643.
2013 Jagannathan, V., Bannoehr, J., Plattet, P., Hauswirth, R., Drögemüller, C., Drögemüller, M., Wiener, D.J., Doherr, M., Owczarek-Lipska, M., Galichet, A., Welle, M.M., Tengvall, K., Bergvall, K., Lohi, H., Rüfenacht, S., Linek, M., Paradis, M., Müller, E.J., Roosje, P., Leeb, T. :
A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte differentiation. PLoS Genet 9:e1003848, 2013. Pubmed reference: 24098150. DOI: 10.1371/journal.pgen.1003848.
2003 Page, N., Paradis, M., Lapointe, J.M., Dunstan, R.W. :
Hereditary nasal parakeratosis in Labrador Retrievers Veterinary Dermatology 14:103-10, 2003. Pubmed reference: 12662268.
Peters, J., Scott, D.W., Erb, H.N., Miller, W.H. :
Hereditary nasal parakeratosis in Labrador retrievers: 11 new cases and a retrospective study on the presence of accumulations of serum ('serum lakes') in the epidermis of parakeratotic dermatoses and inflamed nasal plana of dogs Veterinary Dermatology 14:197-203, 2003. Pubmed reference: 12895224.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 13 Oct 2013
  • Changed by Frank Nicholas on 15 Feb 2018