NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi
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 inv...
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ftmdpi:oai:mdpi.com:/2073-4425/11/11/1297/ 2023-08-20T04:05:48+02:00 NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi Matthias Christen Michaela Austel Frane Banovic Vidhya Jagannathan Tosso Leeb agris 2020-10-30 application/pdf https://doi.org/10.3390/genes11111297 EN eng Multidisciplinary Digital Publishing Institute Animal Genetics and Genomics https://dx.doi.org/10.3390/genes11111297 https://creativecommons.org/licenses/by/4.0/ Genes; Volume 11; Issue 11; Pages: 1297 Canis lupus familiaris animal model genodermatosis dermatology skin CHILD syndrome ILVEN epidermal nevus precision medicine Text 2020 ftmdpi https://doi.org/10.3390/genes11111297 2023-08-01T00:22:58Z 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. Text Canis lupus MDPI Open Access Publishing Genes 11 11 1297 |
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MDPI Open Access Publishing |
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English |
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Canis lupus familiaris animal model genodermatosis dermatology skin CHILD syndrome ILVEN epidermal nevus precision medicine |
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Canis lupus familiaris animal model genodermatosis dermatology skin CHILD syndrome ILVEN epidermal nevus precision medicine Matthias Christen Michaela Austel Frane Banovic Vidhya Jagannathan Tosso Leeb NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi |
topic_facet |
Canis lupus familiaris animal model genodermatosis dermatology skin CHILD syndrome ILVEN epidermal nevus precision medicine |
description |
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. |
format |
Text |
author |
Matthias Christen Michaela Austel Frane Banovic Vidhya Jagannathan Tosso Leeb |
author_facet |
Matthias Christen Michaela Austel Frane Banovic Vidhya Jagannathan Tosso Leeb |
author_sort |
Matthias Christen |
title |
NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi |
title_short |
NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi |
title_full |
NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi |
title_fullStr |
NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi |
title_full_unstemmed |
NSDHL Frameshift Deletion in a Mixed Breed Dog with Progressive Epidermal Nevi |
title_sort |
nsdhl frameshift deletion in a mixed breed dog with progressive epidermal nevi |
publisher |
Multidisciplinary Digital Publishing Institute |
publishDate |
2020 |
url |
https://doi.org/10.3390/genes11111297 |
op_coverage |
agris |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_source |
Genes; Volume 11; Issue 11; Pages: 1297 |
op_relation |
Animal Genetics and Genomics https://dx.doi.org/10.3390/genes11111297 |
op_rights |
https://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.3390/genes11111297 |
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Genes |
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11 |
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11 |
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1297 |
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1774716543298437120 |