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Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion
Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to descr...
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/PMC8509745/ https://www.ncbi.nlm.nih.gov/pubmed/34640625 http://dx.doi.org/10.3390/jcm10194608 |
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author | Cabrera-Borrego, Eva Montero-Vilchez, Trinidad Bermúdez-Jiménez, Francisco José Tercedor-Sánchez, Jesús Tercedor-Sánchez, Luis Sánchez-Díaz, Manuel Macías-Ruiz, Rosa Molina-Jiménez, María Cañizares-García, Francisco Javier Fernández-Segura, Eduardo Fernandez-Flores, Angel Arias-Santiago, Salvador Jiménez-Jáimez, Juan |
author_facet | Cabrera-Borrego, Eva Montero-Vilchez, Trinidad Bermúdez-Jiménez, Francisco José Tercedor-Sánchez, Jesús Tercedor-Sánchez, Luis Sánchez-Díaz, Manuel Macías-Ruiz, Rosa Molina-Jiménez, María Cañizares-García, Francisco Javier Fernández-Segura, Eduardo Fernandez-Flores, Angel Arias-Santiago, Salvador Jiménez-Jáimez, Juan |
author_sort | Cabrera-Borrego, Eva |
collection | PubMed |
description | Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram. |
format | Online Article Text |
id | pubmed-8509745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85097452021-10-13 Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion Cabrera-Borrego, Eva Montero-Vilchez, Trinidad Bermúdez-Jiménez, Francisco José Tercedor-Sánchez, Jesús Tercedor-Sánchez, Luis Sánchez-Díaz, Manuel Macías-Ruiz, Rosa Molina-Jiménez, María Cañizares-García, Francisco Javier Fernández-Segura, Eduardo Fernandez-Flores, Angel Arias-Santiago, Salvador Jiménez-Jáimez, Juan J Clin Med Article Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram. MDPI 2021-10-08 /pmc/articles/PMC8509745/ /pubmed/34640625 http://dx.doi.org/10.3390/jcm10194608 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 Cabrera-Borrego, Eva Montero-Vilchez, Trinidad Bermúdez-Jiménez, Francisco José Tercedor-Sánchez, Jesús Tercedor-Sánchez, Luis Sánchez-Díaz, Manuel Macías-Ruiz, Rosa Molina-Jiménez, María Cañizares-García, Francisco Javier Fernández-Segura, Eduardo Fernandez-Flores, Angel Arias-Santiago, Salvador Jiménez-Jáimez, Juan Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion |
title | Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion |
title_full | Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion |
title_fullStr | Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion |
title_full_unstemmed | Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion |
title_short | Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion |
title_sort | heterozygous arrhythmogenic cardiomyopathy-desmoplakin mutation carriers exhibit a subclinical cutaneous phenotype with cell membrane disruption and lack of intercellular adhesion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509745/ https://www.ncbi.nlm.nih.gov/pubmed/34640625 http://dx.doi.org/10.3390/jcm10194608 |
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