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A de novo variant in the ASPRV1 gene in a dog with ichthyosis

Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key pl...

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Autores principales: Bauer, Anina, Waluk, Dominik P., Galichet, Arnaud, Timm, Katrin, Jagannathan, Vidhya, Sayar, Beyza S., Wiener, Dominique J., Dietschi, Elisabeth, Müller, Eliane J., Roosje, Petra, Welle, Monika M., Leeb, Tosso
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352138/
https://www.ncbi.nlm.nih.gov/pubmed/28249031
http://dx.doi.org/10.1371/journal.pgen.1006651
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author Bauer, Anina
Waluk, Dominik P.
Galichet, Arnaud
Timm, Katrin
Jagannathan, Vidhya
Sayar, Beyza S.
Wiener, Dominique J.
Dietschi, Elisabeth
Müller, Eliane J.
Roosje, Petra
Welle, Monika M.
Leeb, Tosso
author_facet Bauer, Anina
Waluk, Dominik P.
Galichet, Arnaud
Timm, Katrin
Jagannathan, Vidhya
Sayar, Beyza S.
Wiener, Dominique J.
Dietschi, Elisabeth
Müller, Eliane J.
Roosje, Petra
Welle, Monika M.
Leeb, Tosso
author_sort Bauer, Anina
collection PubMed
description Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding “aspartic peptidase, retroviral-like 1”, which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.
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spelling pubmed-53521382017-04-06 A de novo variant in the ASPRV1 gene in a dog with ichthyosis Bauer, Anina Waluk, Dominik P. Galichet, Arnaud Timm, Katrin Jagannathan, Vidhya Sayar, Beyza S. Wiener, Dominique J. Dietschi, Elisabeth Müller, Eliane J. Roosje, Petra Welle, Monika M. Leeb, Tosso PLoS Genet Research Article Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding “aspartic peptidase, retroviral-like 1”, which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses. Public Library of Science 2017-03-01 /pmc/articles/PMC5352138/ /pubmed/28249031 http://dx.doi.org/10.1371/journal.pgen.1006651 Text en © 2017 Bauer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bauer, Anina
Waluk, Dominik P.
Galichet, Arnaud
Timm, Katrin
Jagannathan, Vidhya
Sayar, Beyza S.
Wiener, Dominique J.
Dietschi, Elisabeth
Müller, Eliane J.
Roosje, Petra
Welle, Monika M.
Leeb, Tosso
A de novo variant in the ASPRV1 gene in a dog with ichthyosis
title A de novo variant in the ASPRV1 gene in a dog with ichthyosis
title_full A de novo variant in the ASPRV1 gene in a dog with ichthyosis
title_fullStr A de novo variant in the ASPRV1 gene in a dog with ichthyosis
title_full_unstemmed A de novo variant in the ASPRV1 gene in a dog with ichthyosis
title_short A de novo variant in the ASPRV1 gene in a dog with ichthyosis
title_sort de novo variant in the asprv1 gene in a dog with ichthyosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352138/
https://www.ncbi.nlm.nih.gov/pubmed/28249031
http://dx.doi.org/10.1371/journal.pgen.1006651
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