Genetic variant in the NSDHL gene in a cat with multiple congenital lesions resembling inflammatory linear verrucous epidermal nevi

Abstract

Background The feline counterpart of human inflammatory linear verrucous epidermal nevus (ILVEN) has been described; however, the possible underlying developmental defect has not been investigated. Objective To report a case of multiple ILVEN‐like lesions in a cat with a genetic variant in the NSDHL gene. Animals 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. Methods and results According to the clinical and histopathological findings, a diagnosis of multiple ILVEN‐like lesions was made. Genetic investigation revealed a heterozygous missense variant in the X‐chromosomal NSDHL gene predicted to lead to a loss‐of‐function of the NSDHL protein. Conclusions and clinical importance To the best of the authors’ knowledge, this is the first case of feline ILVEN‐like lesions in which a genetic cause has been proposed. Future studies to establish a causal relationship between NSDHL variants and skin lesions might lead to pathogenesis‐directed treatments.

NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi

“…As clinical and histopathological findings resembled previously published companion animals with congenital epidermal nevi [10][11][12], we hypothesized that the phenotype in the affected dog was due to a heterozygous variant in the NSDHL gene. Hence, NSDHL was investigated as the top functional candidate gene.…”

“…In this study, we identified a heterozygous NSDHL: c.718_722delGAACA frameshift variant in a mixed breed dog with a severe form of progressive epidermal nevi. The NSDHL gene encodes the enzyme NAD(P) dependent steroid dehydrogenase-like, which is involved in cholesterol biosynthesis and has been associated with human CHILD syndrome [8], as well as canine and feline congenital epidermal nevi [10][11][12].…”

“…Genes 2020, 11, 1297 2 of 8 congenital epidermal nevi without limb defects and candidate causative variants in the NSDHL gene have been described in two Labrador Retrievers [10], one purebred Chihuahua [11], and one cat [12] (OMIA 002117-9615, 002117-9685).…”

“…In a continuation of our earlier studies [10][11][12], the present study aimed to characterize the clinical and histopathological phenotype in a female Chihuahua cross with congenital progressive epidermal nevi and to identify the likely causative genetic variant.…”

X‐linked cutaneous mosaicism in a dog

“…1 So far, only a limited number of X-linked genodermatoses characterized by cutaneous mosaicism have been recognized in domestic animals. [3][4][5][6][7] We have described an X-linked semidominant congenital cornification defect in a 7-month-old female Labrador retriever-cross dog showing cutaneous mosaicism. 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 (Figure 1a,b).…”