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First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses

Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development...

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Autores principales: Diociaiuti, Andrea, Castiglia, Daniele, Corbeddu, Marialuisa, Rotunno, Roberta, Rossi, Sabrina, Pisaneschi, Elisa, Cesario, Claudia, Condorelli, Angelo Giuseppe, Zambruno, Giovanna, El Hachem, May
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593923/
https://www.ncbi.nlm.nih.gov/pubmed/33081034
http://dx.doi.org/10.3390/ijms21207707
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author Diociaiuti, Andrea
Castiglia, Daniele
Corbeddu, Marialuisa
Rotunno, Roberta
Rossi, Sabrina
Pisaneschi, Elisa
Cesario, Claudia
Condorelli, Angelo Giuseppe
Zambruno, Giovanna
El Hachem, May
author_facet Diociaiuti, Andrea
Castiglia, Daniele
Corbeddu, Marialuisa
Rotunno, Roberta
Rossi, Sabrina
Pisaneschi, Elisa
Cesario, Claudia
Condorelli, Angelo Giuseppe
Zambruno, Giovanna
El Hachem, May
author_sort Diociaiuti, Andrea
collection PubMed
description Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation.
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spelling pubmed-75939232020-10-30 First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses Diociaiuti, Andrea Castiglia, Daniele Corbeddu, Marialuisa Rotunno, Roberta Rossi, Sabrina Pisaneschi, Elisa Cesario, Claudia Condorelli, Angelo Giuseppe Zambruno, Giovanna El Hachem, May Int J Mol Sci Article Keratinopathic ichthyoses (KI) are a clinically heterogeneous group of keratinization disorders due to mutations in KRT1, KTR10, or KRT2 genes encoding keratins of suprabasal epidermis. Characteristic clinical features include superficial blisters and erosions in infancy and progressive development of hyperkeratosis. Histopathology shows epidermolytic hyperkeratosis. We describe the clinical, histopathological, and molecular findings of a series of 26 Italian patients from 19 unrelated families affected with (i) epidermolytic ichthyosis due to KRT1 or KRT10 mutations (7 and 9 cases, respectively); (ii) KTR10-mutated ichthyosis with confetti (2 cases); (iii) KRT2-mutated superficial epidermolytic ichthyosis (5 cases); and (iv) KRT10-mutated epidermolytic nevus (2 cases). Of note, molecular genetic testing in a third case of extensive epidermolytic nevus revealed a somatic missense mutation (p.Asn186Asp) in the KRT2 gene, detected in DNA from lesional skin at an allelic frequency of 25% and, at very low frequency (1.5%), also in blood. Finally, we report three novel dominant mutations, including a frameshift mutation altering the C-terminal V2 domain of keratin 1 in three familiar cases presenting a mild phenotype. Overall, our findings expand the phenotypic and molecular spectrum of KI and show for the first time that epidermolytic nevus can be due to somatic KRT2 mutation. MDPI 2020-10-18 /pmc/articles/PMC7593923/ /pubmed/33081034 http://dx.doi.org/10.3390/ijms21207707 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Diociaiuti, Andrea
Castiglia, Daniele
Corbeddu, Marialuisa
Rotunno, Roberta
Rossi, Sabrina
Pisaneschi, Elisa
Cesario, Claudia
Condorelli, Angelo Giuseppe
Zambruno, Giovanna
El Hachem, May
First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
title First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
title_full First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
title_fullStr First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
title_full_unstemmed First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
title_short First Case of KRT2 Epidermolytic Nevus and Novel Clinical and Genetic Findings in 26 Italian Patients with Keratinopathic Ichthyoses
title_sort first case of krt2 epidermolytic nevus and novel clinical and genetic findings in 26 italian patients with keratinopathic ichthyoses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593923/
https://www.ncbi.nlm.nih.gov/pubmed/33081034
http://dx.doi.org/10.3390/ijms21207707
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