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Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome

Tissue fragility, skin hyperextensibility and joint hypermobility are defining characteristics of Ehlers–Danlos syndrome (EDS). Human EDS is subclassified into fourteen types including dermatosparactic EDS, characterized by extreme skin fragility and caused by biallelic ADAMTS2 mutations. We report...

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Autores principales: Jaffey, Jared A., Bullock, Garrett, Guo, Juyuan, Mhlanga-Mutangadura, Tendai, O’Brien, Dennis P., Coates, Joan R., Morrissey, Rochelle, Hutchison, Robert, Donnelly, Kevin S., Cohn, Leah A., Katz, Martin L., Johnson, Gary S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690363/
https://www.ncbi.nlm.nih.gov/pubmed/36421833
http://dx.doi.org/10.3390/genes13112158
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author Jaffey, Jared A.
Bullock, Garrett
Guo, Juyuan
Mhlanga-Mutangadura, Tendai
O’Brien, Dennis P.
Coates, Joan R.
Morrissey, Rochelle
Hutchison, Robert
Donnelly, Kevin S.
Cohn, Leah A.
Katz, Martin L.
Johnson, Gary S.
author_facet Jaffey, Jared A.
Bullock, Garrett
Guo, Juyuan
Mhlanga-Mutangadura, Tendai
O’Brien, Dennis P.
Coates, Joan R.
Morrissey, Rochelle
Hutchison, Robert
Donnelly, Kevin S.
Cohn, Leah A.
Katz, Martin L.
Johnson, Gary S.
author_sort Jaffey, Jared A.
collection PubMed
description Tissue fragility, skin hyperextensibility and joint hypermobility are defining characteristics of Ehlers–Danlos syndrome (EDS). Human EDS is subclassified into fourteen types including dermatosparactic EDS, characterized by extreme skin fragility and caused by biallelic ADAMTS2 mutations. We report two novel, ADAMTS2 variants in DNA from EDS-affected dogs. Separate whole-genome sequences from a Pit Bull Terrier and an Alapaha Blue Blood Bulldog each contained a rare, homozygous variant (11:2280117delC, CanFam3.1), predicted to produce a frameshift in the transcript from the first coding ADAMTS2 exon (c.10delC) and a severely truncated protein product, p.(Pro4ArgfsTer175). The clinical features of these dogs and 4 others with the same homozygous deletion included multifocal wounds, atrophic scars, joint hypermobility, narrowed palpebral fissures, skin hyperextensibility, and joint-associated swellings. Due to severe skin fragility, the owners of all 6 dogs elected euthanasia before the dogs reached 13 weeks of age. Cross sections of collagen fibrils in post-mortem dermal tissues from 2 of these dogs showed hieroglyphic-like figures similar to those from cases of severe dermatosparaxis in other species. The whole-genome sequence from an adult Catahoula Leopard Dog contained a homozygous ADAMTS2 missense mutation, [11:2491238G>A; p.(Arg966His)]. This dog exhibited multifocal wounds, atrophic scars, and joint hypermobility, but has survived for at least 9 years. This report expands the spectrum of clinical features of the canine dermatosparactic subtype of EDS and illustrates the potential utility of subclassifying canine EDS by the identity of gene harboring the causal variant.
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spelling pubmed-96903632022-11-25 Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome Jaffey, Jared A. Bullock, Garrett Guo, Juyuan Mhlanga-Mutangadura, Tendai O’Brien, Dennis P. Coates, Joan R. Morrissey, Rochelle Hutchison, Robert Donnelly, Kevin S. Cohn, Leah A. Katz, Martin L. Johnson, Gary S. Genes (Basel) Article Tissue fragility, skin hyperextensibility and joint hypermobility are defining characteristics of Ehlers–Danlos syndrome (EDS). Human EDS is subclassified into fourteen types including dermatosparactic EDS, characterized by extreme skin fragility and caused by biallelic ADAMTS2 mutations. We report two novel, ADAMTS2 variants in DNA from EDS-affected dogs. Separate whole-genome sequences from a Pit Bull Terrier and an Alapaha Blue Blood Bulldog each contained a rare, homozygous variant (11:2280117delC, CanFam3.1), predicted to produce a frameshift in the transcript from the first coding ADAMTS2 exon (c.10delC) and a severely truncated protein product, p.(Pro4ArgfsTer175). The clinical features of these dogs and 4 others with the same homozygous deletion included multifocal wounds, atrophic scars, joint hypermobility, narrowed palpebral fissures, skin hyperextensibility, and joint-associated swellings. Due to severe skin fragility, the owners of all 6 dogs elected euthanasia before the dogs reached 13 weeks of age. Cross sections of collagen fibrils in post-mortem dermal tissues from 2 of these dogs showed hieroglyphic-like figures similar to those from cases of severe dermatosparaxis in other species. The whole-genome sequence from an adult Catahoula Leopard Dog contained a homozygous ADAMTS2 missense mutation, [11:2491238G>A; p.(Arg966His)]. This dog exhibited multifocal wounds, atrophic scars, and joint hypermobility, but has survived for at least 9 years. This report expands the spectrum of clinical features of the canine dermatosparactic subtype of EDS and illustrates the potential utility of subclassifying canine EDS by the identity of gene harboring the causal variant. MDPI 2022-11-19 /pmc/articles/PMC9690363/ /pubmed/36421833 http://dx.doi.org/10.3390/genes13112158 Text en © 2022 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
Jaffey, Jared A.
Bullock, Garrett
Guo, Juyuan
Mhlanga-Mutangadura, Tendai
O’Brien, Dennis P.
Coates, Joan R.
Morrissey, Rochelle
Hutchison, Robert
Donnelly, Kevin S.
Cohn, Leah A.
Katz, Martin L.
Johnson, Gary S.
Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome
title Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome
title_full Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome
title_fullStr Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome
title_full_unstemmed Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome
title_short Novel Homozygous ADAMTS2 Variants and Associated Disease Phenotypes in Dogs with Dermatosparactic Ehlers–Danlos Syndrome
title_sort novel homozygous adamts2 variants and associated disease phenotypes in dogs with dermatosparactic ehlers–danlos syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9690363/
https://www.ncbi.nlm.nih.gov/pubmed/36421833
http://dx.doi.org/10.3390/genes13112158
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