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A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica
In a litter of Turkish Van cats, three out of six kittens developed severe signs of skin disease, diarrhea, and systemic signs of stunted growth at 6 weeks of age. Massive secondary infections of the skin lesions evolved. Histopathological examinations showed a mild to moderate hyperplastic epidermi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469226/ https://www.ncbi.nlm.nih.gov/pubmed/34573291 http://dx.doi.org/10.3390/genes12091309 |
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author | Kiener, Sarah Cikota, Robert Welle, Monika Jagannathan, Vidhya Åhman, Susanne Leeb, Tosso |
author_facet | Kiener, Sarah Cikota, Robert Welle, Monika Jagannathan, Vidhya Åhman, Susanne Leeb, Tosso |
author_sort | Kiener, Sarah |
collection | PubMed |
description | In a litter of Turkish Van cats, three out of six kittens developed severe signs of skin disease, diarrhea, and systemic signs of stunted growth at 6 weeks of age. Massive secondary infections of the skin lesions evolved. Histopathological examinations showed a mild to moderate hyperplastic epidermis, covered by a thick layer of laminar to compact, mostly parakeratotic keratin. The dermis was infiltrated with moderate amounts of lymphocytes and plasma cells. Due to the severity of the clinical signs, one affected kitten died and the other two had to be euthanized. We sequenced the genome of one affected kitten and compared the data to 54 control genomes. A search for private variants in the two candidate genes for the observed phenotype, MKLN1 and SLC39A4, revealed a single protein-changing variant, SLC39A4:c.1057G>C or p.Gly353Arg. The solute carrier family 39 member 4 gene (SLC39A4) encodes an intestinal zinc transporter required for the uptake of dietary zinc. The variant is predicted to change a highly conserved glycine residue within the first transmembrane domain, which most likely leads to a loss of function. The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 173 unrelated control cats. Together with the knowledge on the effects of SLC39A4 variants in other species, these data suggest SLC39A4:c.1057G>C as candidate causative genetic variant for the phenotype in the investigated kittens. In line with the human phenotype, we propose to designate this disease acrodermatitis enteropathica (AE). |
format | Online Article Text |
id | pubmed-8469226 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84692262021-09-27 A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica Kiener, Sarah Cikota, Robert Welle, Monika Jagannathan, Vidhya Åhman, Susanne Leeb, Tosso Genes (Basel) Article In a litter of Turkish Van cats, three out of six kittens developed severe signs of skin disease, diarrhea, and systemic signs of stunted growth at 6 weeks of age. Massive secondary infections of the skin lesions evolved. Histopathological examinations showed a mild to moderate hyperplastic epidermis, covered by a thick layer of laminar to compact, mostly parakeratotic keratin. The dermis was infiltrated with moderate amounts of lymphocytes and plasma cells. Due to the severity of the clinical signs, one affected kitten died and the other two had to be euthanized. We sequenced the genome of one affected kitten and compared the data to 54 control genomes. A search for private variants in the two candidate genes for the observed phenotype, MKLN1 and SLC39A4, revealed a single protein-changing variant, SLC39A4:c.1057G>C or p.Gly353Arg. The solute carrier family 39 member 4 gene (SLC39A4) encodes an intestinal zinc transporter required for the uptake of dietary zinc. The variant is predicted to change a highly conserved glycine residue within the first transmembrane domain, which most likely leads to a loss of function. The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 173 unrelated control cats. Together with the knowledge on the effects of SLC39A4 variants in other species, these data suggest SLC39A4:c.1057G>C as candidate causative genetic variant for the phenotype in the investigated kittens. In line with the human phenotype, we propose to designate this disease acrodermatitis enteropathica (AE). MDPI 2021-08-25 /pmc/articles/PMC8469226/ /pubmed/34573291 http://dx.doi.org/10.3390/genes12091309 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kiener, Sarah Cikota, Robert Welle, Monika Jagannathan, Vidhya Åhman, Susanne Leeb, Tosso A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica |
title | A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica |
title_full | A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica |
title_fullStr | A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica |
title_full_unstemmed | A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica |
title_short | A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica |
title_sort | missense variant in slc39a4 in a litter of turkish van cats with acrodermatitis enteropathica |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469226/ https://www.ncbi.nlm.nih.gov/pubmed/34573291 http://dx.doi.org/10.3390/genes12091309 |
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