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

Christen, Matthias; Austel, Michaela; Banovic, Frane; Jagannathan, Vidhya; Leeb, Tosso (2020). NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi. Genes, 11(11) MDPI, Molecular Diversity Preservation International 10.3390/genes11111297

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Loss-of-function variants in the NSDHL gene have been associated with epidermal nevi in humans with congenital hemidysplasia, ichthyosiform nevi, and limb defects (CHILD) syndrome and in companion animals. The NSDHL gene codes for the NAD(P)-dependent steroid dehydrogenase-like protein, which is involved in cholesterol biosynthesis. In this study, a female Chihuahua cross with a clinical and histological phenotype consistent with progressive epidermal nevi is presented. All exons of the NSDHL candidate gene were amplified by PCR and analyzed by Sanger sequencing. A heterozygous frameshift variant, c.718_722delGAACA, was identified in the affected dog. In lesional skin, the vast majority of NSDHL transcripts lacked the five deleted bases. The variant is predicted to produce a premature stop codon truncating 34% of the encoded protein, p.Glu240Profs*17. The mutant allele was absent from 22 additionally genotyped Chihuahuas, as well as from 647 control dogs of diverse breeds and eight wolves. The available experimental data together with current knowledge about NSDHL variants and their functional impact in humans, dogs, and other species prompted us to classify this variant as pathogenic according to the ACMG guidelines that were previously established for human sequence variants. Therefore, we propose the c.718_722delGAACA variant as causative variant for the observed skin lesions in this dog.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > DermFocus
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Christen, Matthias Theo; Jagannathan, Vidya and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2073-4425

Publisher:

MDPI, Molecular Diversity Preservation International

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

11 Nov 2020 10:25

Last Modified:

11 Nov 2020 10:25

Publisher DOI:

10.3390/genes11111297

PubMed ID:

33143176

Uncontrolled Keywords:

CHILD syndrome Canis lupus familiaris ILVEN animal model dermatology epidermal nevus genodermatosis precision medicine skin

BORIS DOI:

10.7892/boris.147845

URI:

https://boris.unibe.ch/id/eprint/147845

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