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Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma
Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has bee...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379359/ https://www.ncbi.nlm.nih.gov/pubmed/37510397 http://dx.doi.org/10.3390/genes14071494 |
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author | González-Quintana, Adrián Garrido-Moraga, Rocío Palencia-Pérez, Sara I. Hernández-Martín, Ángela Sánchez-Munárriz, Jon Lezana-Rosales, José M. Quesada-Espinosa, Juan F. Martín, Miguel A. Arteche-López, Ana |
author_facet | González-Quintana, Adrián Garrido-Moraga, Rocío Palencia-Pérez, Sara I. Hernández-Martín, Ángela Sánchez-Munárriz, Jon Lezana-Rosales, José M. Quesada-Espinosa, Juan F. Martín, Miguel A. Arteche-López, Ana |
author_sort | González-Quintana, Adrián |
collection | PubMed |
description | Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene–clinical feature associations. |
format | Online Article Text |
id | pubmed-10379359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103793592023-07-29 Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma González-Quintana, Adrián Garrido-Moraga, Rocío Palencia-Pérez, Sara I. Hernández-Martín, Ángela Sánchez-Munárriz, Jon Lezana-Rosales, José M. Quesada-Espinosa, Juan F. Martín, Miguel A. Arteche-López, Ana Genes (Basel) Brief Report Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene–clinical feature associations. MDPI 2023-07-22 /pmc/articles/PMC10379359/ /pubmed/37510397 http://dx.doi.org/10.3390/genes14071494 Text en © 2023 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 | Brief Report González-Quintana, Adrián Garrido-Moraga, Rocío Palencia-Pérez, Sara I. Hernández-Martín, Ángela Sánchez-Munárriz, Jon Lezana-Rosales, José M. Quesada-Espinosa, Juan F. Martín, Miguel A. Arteche-López, Ana Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma |
title | Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma |
title_full | Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma |
title_fullStr | Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma |
title_full_unstemmed | Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma |
title_short | Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma |
title_sort | integration of phenotype term prioritization and gene expression analysis reveals a novel variant in the perp gene associated with autosomal recessive erythrokeratoderma |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379359/ https://www.ncbi.nlm.nih.gov/pubmed/37510397 http://dx.doi.org/10.3390/genes14071494 |
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