A missense variant in the NSDHL gene in a Chihuahua with a congenital cornification disorder resembling inflammatory linear verrucous epidermal nevi. (1st October 2019)

• Record Type: Journal Article
• Authors: Leuthard, F.; Lehner, G.; Jagannathan, V.; Leeb, T.; Welle, M.
• Is Part Of: Animal genetics. Volume 50:Number 6(2019)
• Page Start: 768
• Page End: 771
• Publication Date: 2019-10-01
• Subjects: Canis lupus familiaris -- dermatology -- genodermatosis -- precision medicine -- skin -- X‐chromosome; Animal genetics -- Periodicals; 572.8
• DOI: 10.1111/age.12862
• Languages: English
• ISSNs: 0268-9146

Abstract

Summary: Congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome in humans is a genodermatosis characterized by inflammatory linear verrucous epidermal nevi (ILVEN), often showing a striking lateralization pattern. It is caused by variants in the NSDHL gene encoding a 3β‐hydroxysteroid dehydrogenase involved in the cholesterol biosynthesis pathway. In the present study, we investigated a female Chihuahua, which showed clinical and histological signs of ILVEN. We performed a candidate gene analysis in the affected animal. This analysis revealed a single missense variant in the NSDHL gene in the affected dog (XM_014111859.2:c.700G>A). The variant is predicted to cause a non‐conservative amino acid change from glycine to arginine, XP_013967334.1:p.(Gly234Arg). The mutant allele was absent from WGS data of 594 genetically diverse dogs and eight wolves. Sanger sequencing confirmed that the variant was heterozygous in the affected dog and absent from 22 control Chihuahuas. Based on the knowledge about the functional impact of NSDHL variants in dogs and other species, c.700G>A is probably pathogenic and a convincing candidate causative variant for the observed skin lesions in the affected Chihuahua.