OMIA 002117-9615 : Verrucous epidermal keratinocytic nevi in Canis lupus familiaris
The trait is embryonic lethal in hemizygous mutant males (Bauer et al. 2017).Mapping: "Visual inspection of candidate genes located on the X-chromosome" enabled Bauer et al. (2017) to identify "a large deletion in the NSDHL gene, encoding NAD(P) dependent steroid dehydrogenase-like, a 3β-hydroxysteroid dehydrogenase involved in cholesterol biosynthesis." Molecular basis: Bauer et al. (2017):"a deletion spanning 14,399 bp including the last three exons of the NSDHL gene . . . . The formal variant designation is chrX:120,749,179_120,763,577del14,399".
Leuthard et al. (2019) detected a heterozygous missense variant in NSDHL in a female affected Chihuahua, c.700G>A or p.Gly234Arg.
Christen et al. (2020): "A heterozygous frameshift variant, c.718_722delGAACA, was identified in . . . a female Chihuahua cross with a clinical and histological phenotype consistent with progressive epidermal nevi"Clinical features: Bauer et al. (2017):"No abnormalities were found on the affected daughter during general physical examination except a stunted growth. Linear hyperplastic and partially alopecic lesions, covered with thick brown scales and clusters of dilated follicular ostia were the most prominent dermatological features (Figure 1). The lesions were distributed along Blaschko’s lines in a bilateral rather symmetrical fashion and were more evident on the limbs, the head, the neck and the dorsal trunk. The abdominal and inguinal skin appeared normal. Frond like hyperkeratotic lesions at the margin of all the pawpads with occasional horn-like projections were considered the most probable cause of the visible lameness. Cytological examination of the linear hyperplastic lesions, revealed the presence of variable numbers of coccoid bacteria and a large number of Malassezia yeasts which were suspected to substantially contribute to the pruritus and the offensive odor. Results of the blood tests and urinalysis were unremarkable."
De Lucia et al. (2019): "Alopecic scaly plaques following the Blaschko’s lines on the limbs, the head, the dorsal neck and the trunk, and severe foot pads hyperkeratosis were the most relevant lesions"Pathology: Bauer et al. (2017):"The histopathological findings were identical in all biopsies . . . . Multifocally, the epidermis and the wall of the hair follicular infundibuli were moderately to severely hyperplastic with abrupt transition to normal skin. Within the hyperplastic area the infundibular epithelium was covered by thick layers of densely packed parakeratotickeratin which was distending the infundibuli. The parakeratotic keratin was often protruding above the epidermal surface. The size of the keratohyalin granules within the granular cell layers of the epidermis and the infundibular wall was within the normal range. Within the parakeratotic keratin, multifocally variable numbers of coccoid bacteria were present and occasionally the lumen of infundibuli contained degenerate neutrophils. Sebaceous glands appeared normal. The interfollicular epidermis was covered by moderate to large amounts of laminar to compact mostly orthokeratotic, but also some parakeratotic keratin. Within the keratin layers of the epidermis multifocally degenerate neutrophils, nuclear debris and small numbers of coccoid bacteria were present. Multifocally exocytosis of neutrophils was seen. Within the superficial dermis there was a mild pigmentary incontinence and a moderate perivascular infiltrate composed of neutrophils, mast cells and fewer lymphocytes." Breeds: Chihuahua, Labrador Retriever, Mixed breed. Associated gene:
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|NSDHL||NAD(P) dependent steroid dehydrogenase-like||Canis lupus familiaris||X||NC_051843.1 (122944801..122978966)||NSDHL||Homologene, Ensembl, NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|790||Labrador Retriever||CHILD-like syndrome||NSDHL||deletion, gross (>20)||Naturally occurring variant||CanFam3.1||X||g.120749179_120763577del||c.507+220_*9662del||XM_005641965.1; deletion of 14,399bp||2017||28739597|
|1243||Chihuahua||Verrucous epidermal keratinocytic nevi||NSDHL||missense||Naturally occurring variant||CanFam3.1||X||g.120752468G>A||c.700G>A||p.(G234R)||CanFam3.1 ChrX:120,752,468G>A; XM_014111859.2:c.700G>A; XP_013967334.1: p.Gly234Arg||2019||31571289|
|1268||Chihuahua||Verrucous epidermal keratinocytic nevi||NSDHL||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||X||g.120752486_120752490del||c.718_722delGAACA||p.(E240Pfs*17)||NC_006621.3: g.120,752,486_120,752,490delGAACA; XM_014111859.2:c.718_722delGAACA; XP_013967334.1:p.(Glu240Profs*17) (Christen et al., 2020)||2020||33143176|
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.
|2021||Mauldin, E.A., Elias, P.M. :|
|Ichthyosis and hereditary cornification disorders in dogs. Vet Dermatol 32:567-e154, 2021. Pubmed reference: 34796560. DOI: 10.1111/vde.13033.|
|2020||Christen, M., Austel, M., Banovic, F., Jagannathan, V., Leeb, T. :|
|NSDHL frameshift deletion in a mixed breed dog with progressive epidermal nevi. Genes (Basel) 11:1297, 2020. Pubmed reference: 33143176. DOI: 10.3390/genes11111297.|
|2019||De Lucia, M., Angileri, M., Bauer, A., Spycher, M., Jaggannathan, V., Denti, D., Di Diodoro, F., Ferro, S., Mezzalira, G., Welle, M., Leeb, T., De Lucia, M., Angileri, M., Bauer, A., Spycher, M., Jaggannathan, V., Denti, D., Di Diodoro, F., Ferro, S., Mezzalira, G., Welle, M., Leeb, T. :|
|X-linked cutaneous mosaicism in a dog. Vet Dermatol 30:361-362, 2019. Pubmed reference: 31012178. DOI: 10.1111/vde.12748.|
|Leuthard, F., Lehner, G., Jagannathan, V., Leeb, T., Welle, M. :|
|A missense variant in the NSDHL gene in a Chihuahua with a congenital cornification disorder resembling inflammatory linear verrucous epidermal nevi. Anim Genet 50:768-771, 2019. Pubmed reference: 31571289. DOI: 10.1111/age.12862.|
|2017||Bauer, A., De Lucia, M., Jagannathan, V., Mezzalira, G., Casal, M.L., Welle, M.M., Leeb, T. :|
|A large deletion in the NSDHL gene in Labrador Retrievers with a congenital cornification disorder. G3 (Bethesda) 7:3115-3121, 2017. Pubmed reference: 28739597. DOI: 10.1534/g3.117.1124.|
|2008||Cadiergues, M.C., Patel, A., Shearer, D.H., Fermor, R., Miah, S., Hendricks, A. :|
|Cornification defect in the golden retriever: clinical, histopathological, ultrastructural and genetic characterisation. Vet Dermatol 19:120-9, 2008. Pubmed reference: 18477327. DOI: 10.1111/j.1365-3164.2008.00667.x.|
|1998||Lewis, D.T., Messinger, L.M., Ginn, P.E., Ford, M.J. :|
|A hereditary disorder of cornification and multiple congenital defects in five Rottweiler dogs Veterinary Dermatology 9:61-72, 1998. Pubmed reference: 34644958.|
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