OMIA 002117-9685 : Verrucous epidermal keratinocytic nevi in Felis catus

In other species: dog

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 308050 (trait) , 300275 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: X-linked semi-dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: Many alias names exist for the phenotype. They include congenital cornification disorder; CHILD nevi; CHILD-like nevi; ILVEN. The human phenotype resulting from NSDHL loss-of-function variants is termed congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome). CHILD syndrome is characterized by epidermal nevi and striking unilateral limb defects. Animals (cats, dogs, mice) with NSDHL variants have similar epidermal nevi, but so far were never reported to also have the limb defects seen in human CHILD syndrome.

Species-specific description: De Lucia et al. (2019): "Veterinary clinicians should be aware of cutaneous mosaicism and consider X-linked genodermatoses when seeing female cases with segmental cutaneous diseases like the one following the Blaschko’s lines."

Inheritance: De Lucia et al. (2019): "In heterozygous females, with an X-linked dominant or semidominant genodermatosis, . . . random inactivation of the X chromosome is responsible for the development of normal and abnormal skin segments distributed in a mosaic pattern. In fact, normal skin derives from progenitor cells in which the X-chromosome carrying the pathogenic variant has been inactivated, whereas stripes or patches of abnormal skin result from progenitor cells after the inactivation of the wild-type (normal) X-chromosome. X-linked cutaneous mosaicism can be heritable and is normally observed in heterozygous females."

The trait is embryonic lethal in hemizygous mutant males.

Molecular basis: De Lucia et al. (2019): "a heterozygous missense variant in the NSDHL gene: XM_004000985.5:c.397A>G or XP_004001034.1:p.(Ser133Gly). The variant was absent from 93 additional genetically diverse control cats as demonstrated by Sanger sequencing. The variant was predicted to affect the essential serine residue of the catalytic tetrad 109Asn‐133Ser‐160Tyr‐164Lys in the conserved short‐chain dehydrogenase/reductase domain of the feline NSDHL protein and thus most likely leading to a functional inactivation of the protein."

Clinical features: De Lucia et al. (2019): "A 2‐year‐old, female, domestic short hair cat with a history of multiple alopecic, verrucous, hyperpigmented and erythematous skin lesions, following Blaschko's lines on the head, the limbs, the trunk and paw pads." The same authors concluded that the clinical signs of this single cat correspond to the "feline counterpart of human inflammatory linear verrucous epidermal nevus (ILVEN)", which closely resembles a mild form of CHILD syndrome, a disorder caused by mutations in the same gene.

Breed: Domestic Shorthair.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
NSDHL NAD(P) dependent steroid dehydrogenase-like Felis catus X NC_018741.3 (127902522..127932256) NSDHL 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 second, third etc relevant column headers.

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.

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
Domestic Shorthair Inflammatory linear verrucous epidermal nevi NSDHL missense Felis_catus_9.0 X c.397A>G p.(S133G) De Lucia et al. (2019): XM_004000985.5:c.397A>G; XP_004001034.1:p.(Ser133Gly) 2019 30474267

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.
2019 De Lucia, M., Bauer, A., Spycher, M., Jagannathan, V., Romano, E., Welle, M., Leeb, T. :
Genetic variant in the NSDHL gene in a cat with multiple congenital lesions resembling inflammatory linear verrucous epidermal nevi. Vet Dermatol 30:64-e18, 2019. Pubmed reference: 30474267. DOI: 10.1111/vde.12699.
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.
2012 Sato, M., Kariya, K., Matsumoto, M., Itoh, M., Kobayashi, Y., Nishifuji, K., Kamiie, J., Shirota, K. :
Feline epidermal nevi resembling human inflammatory linear verrucous epidermal nevus. J Vet Med Sci 74:1337-9, 2012. Pubmed reference: 22672841.

Edit History


  • Created by Tosso Leeb on 24 Sep 2020
  • Changed by Tosso Leeb on 24 Sep 2020
  • Changed by Tosso Leeb on 11 Nov 2020