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ABHD5 frameshift deletion in Golden Retrievers with ichthyosis
Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210301/ https://www.ncbi.nlm.nih.gov/pubmed/34791225 http://dx.doi.org/10.1093/g3journal/jkab397 |
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author | Kiener, Sarah Wiener, Dominique J Hopke, Kaitlin Diesel, Alison B Jagannathan, Vidhya Mauldin, Elizabeth A Casal, Margret L Leeb, Tosso |
author_facet | Kiener, Sarah Wiener, Dominique J Hopke, Kaitlin Diesel, Alison B Jagannathan, Vidhya Mauldin, Elizabeth A Casal, Margret L Leeb, Tosso |
author_sort | Kiener, Sarah |
collection | PubMed |
description | Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 nonaffected family members delimited a critical interval of ∼12.7 Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14 bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2). |
format | Online Article Text |
id | pubmed-9210301 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92103012022-06-21 ABHD5 frameshift deletion in Golden Retrievers with ichthyosis Kiener, Sarah Wiener, Dominique J Hopke, Kaitlin Diesel, Alison B Jagannathan, Vidhya Mauldin, Elizabeth A Casal, Margret L Leeb, Tosso G3 (Bethesda) Investigation Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 nonaffected family members delimited a critical interval of ∼12.7 Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14 bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2). Oxford University Press 2021-11-15 /pmc/articles/PMC9210301/ /pubmed/34791225 http://dx.doi.org/10.1093/g3journal/jkab397 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigation Kiener, Sarah Wiener, Dominique J Hopke, Kaitlin Diesel, Alison B Jagannathan, Vidhya Mauldin, Elizabeth A Casal, Margret L Leeb, Tosso ABHD5 frameshift deletion in Golden Retrievers with ichthyosis |
title |
ABHD5 frameshift deletion in Golden Retrievers with ichthyosis |
title_full |
ABHD5 frameshift deletion in Golden Retrievers with ichthyosis |
title_fullStr |
ABHD5 frameshift deletion in Golden Retrievers with ichthyosis |
title_full_unstemmed |
ABHD5 frameshift deletion in Golden Retrievers with ichthyosis |
title_short |
ABHD5 frameshift deletion in Golden Retrievers with ichthyosis |
title_sort | abhd5 frameshift deletion in golden retrievers with ichthyosis |
topic | Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210301/ https://www.ncbi.nlm.nih.gov/pubmed/34791225 http://dx.doi.org/10.1093/g3journal/jkab397 |
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