Keratin mutations in patients with epidermolysis bullosa simplex: correlations between phenotype severity and disturbance of intermediate filament molecular structure

Jeřábková, Barbora; Marek, Jaromı́r; Bučková, Hana; Kopečková, Lenka; Veselý, Karel; Valíčková, Jana; Fajkus, Jiřı́; Fajkusová, Lenka

doi:10.1111/j.1365-2133.2009.09626.x

Cited by 22 publications

(12 citation statements)

References 49 publications

(58 reference statements)

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“…The most frequent mutation, p.Glu170Lys in KRT5 , according to our findings and data published by others can have various clinical consequences (Ołdak et al 2010 ; Müller et al 2006 ; Jerábková et al 2010 ; Arin et al 2010 ; Yasukawa et al 2002 ). This substitution occurred in five probands of our group.…”

Section: Discussionsupporting

confidence: 80%

“…Both parents were proved to be carriers of p.Glu170Lys (father) or p.Val143Ala (mother), and none of them reported any clinical signs of EBS. Of note, the p.Val143Ala mutation was previously described in the literature, in two patients with autosomal dominant EBS-loc (Jerábková et al 2010 ). Why some p.Glu170Lys and p.Val143Ala heterozygotes do have clinical symptoms of EBS-loc and others do not remains an open question.…”

Section: Discussionmentioning

confidence: 74%

“…We identified mutations in KRT5 or/and KRT14 genes in 38 unrelated patients; that is, on one of the largest published groups of patients (Bolling et al 2011 ; Jerábková et al 2010 ; Chen et al 1995 ; Pfendner et al 2005 ; Arin et al 2010 ). Although around 120 mutations in KRT5 and 95 in KRT14 genes were published so far and patients of Central European origin were also included in other reports, we not only identified recurrent mutations but were also able to find unique and novel ones.…”

Section: Discussionmentioning

confidence: 99%

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Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: further insights into epidemiology and genotype–phenotype correlation

Wertheim–Tysarowska¹,

Ołdak

Giza³

et al. 2015

J Appl Genetics

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Epidermolysis bullosa simplex (EBS) is a hereditary genodermatosis characterised by trauma-induced intraepidermal blistering of the skin. EBS is mostly caused by mutations in the KRT5 and KRT14 genes. Disease severity partially depends on the affected keratin type and may be modulated by mutation type and location. The aim of our study was to identify the molecular defects in KRT5 and KRT14 in a cohort of 46 Polish and one Belarusian probands with clinical suspicion of EBS and to determine the genotype–phenotype correlation. The group of 47 patients with clinical recognition of EBS was enrolled in the study. We analysed all coding exons of KRT5 and KRT14 using Sanger sequencing. The pathogenic status of novel variants was evaluated using bioinformatical tools, control group analysis (DNA from 100 healthy population-matched subjects) and probands’ parents testing. We identified mutations in 80 % of patients and found 29 different mutations, 11 of which were novel and six were found in more than one family. All novel mutations were ascertained as pathogenic. In the majority of cases, the most severe genotype was associated with mutations in highly conserved regions. In some cases, different inheritance mode and clinical significance, than previously reported by others, was observed. We report 11 novel variants and show novel genotype–phenotype correlations. Our data give further insight into the natural history of EBS molecular pathology, epidemiology and mutation origin.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: further insights into epidemiology and genotype–phenotype correlation

Wertheim–Tysarowska¹,

Ołdak

Giza³

et al. 2015

J Appl Genetics

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“…In cattle, suprabasal clefts arise from lysis of the basal keratinocytes and the clumping of the intermediate filaments . The clumping of the intermediate filaments has been described in the Dowling–Meara form of EBS in humans . In cattle, a missense mutation was identified in the KRT5 gene that revealed a one base change (G‐to‐A substitution at position 4164 of the genomic sequence).…”

Section: Epidermolysis Bullosa Simplexmentioning

confidence: 99%

Epidermolysis bullosa in animals: a review

Medeiros

Riet-Correa

2014

Veterinary Dermatology

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Epidermolysis bullosa (EB) is a hereditary mechanobullous disease of animals and humans, characterized by an extreme fragility of the skin and mucous membranes. The main feature of EB in humans and animals is the formation of blisters and erosions in response to minor mechanical trauma. Epidermolysis bullosa is caused by mutations in the genes that code for structural proteins of the cytoskeleton of the basal keratinocytes or of the basement membrane zone. Based on the ultrastructural levels of tissue separation, EB is divided into the following three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. Human types of EB are divided into several subtypes based on their ultrastructural changes and the mode of inheritance; subtypes are not fully established in animals. In humans, it is estimated that EB affects one in 17,000 live births; the frequency of EB in different animals species is not known. In all animal species, except in buffalo with epidermolysis bullosa simplex, multifocal ulcers are observed on the gums, hard and soft palates, mucosa of the lips, cheek mucosa and dorsum of the tongue. Dystrophic or absent nails, a frequent sign seen in human patients with EB, corresponds to the deformities and sloughing of the hooves in ungulates and to dystrophy or atrophy of the claws in dogs and cats. This review covers aspects of the molecular biology, diagnosis, classification, clinical signs and pathology of EB reported in animals.

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“…KRT14, KRT6A, and KRT5 are members of the keratin protein family and are co-expressed during the differentiation process of simple and stratified epithelial tissues (Zhang et al 2014). Furthermore, Jeřábková et al (2010) reported that mutations that occur in these keratin proteins were associated with skin diseases. Zhang et al (2014) used next generation sequencing to study laryngeal squamous cell carcinoma patients and found that KRT14, KRT6A, and KRT5 were part of nine mitochondrial genes (SFN, CTB-63M22.1, HSPB1, KRT5, KRT6A, KRT14, IGHA1, IGLC2, and IGLC3) that were significantly mutated compared to those with healthy tissues.…”

Section: Go Terms Enriched In the Ppi Networkmentioning

confidence: 99%

Construction and Analysis of Protein-Protein Interaction Network to Identify the Molecular Mechanism in Laryngeal Cancer

Harun

Zulkifle

2018

JSM

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Laryngeal cancer is the most common head and neck cancer in the world and its incidence is on the rise. However, the molecular mechanism underlying laryngeal cancer pathogenesis is poorly understood. The goal of this study was to develop a protein-protein interaction (PPI) network for laryngeal cancer to predict the biological pathways that underlie the molecular complexes in the network. Genes involved in laryngeal cancer were extracted from the OMIM database and their interaction partners were identified via text and data mining using Agilent Literature Search, STRING and GeneMANIA. PPI network was then integrated and visualised using Cytoscape ver3.6.0. Molecular complexes in the network were predicted by MCODE plugin and functional enrichment analyses of the molecular complexes were performed using BiNGO. 28 laryngeal cancer-related genes were present in the OMIM database. The PPI network associated with laryngeal cancer contained 161 nodes, 661 edges and five molecular complexes. Some of the complexes were related to the biological behaviour of cancer, providing the foundation for further understanding of the mechanism of laryngeal cancer development and progression.

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Keratin mutations in patients with epidermolysis bullosa simplex: correlations between phenotype severity and disturbance of intermediate filament molecular structure

Abstract: The results of molecular modelling show relationships between patients' phenotypes and the structural effects of individual mutations.

Cited by 22 publications

References 49 publications

Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: further insights into epidemiology and genotype–phenotype correlation

Novel sporadic and recurrent mutations in KRT5 and KRT14 genes in Polish epidermolysis bullosa simplex patients: further insights into epidemiology and genotype–phenotype correlation

Epidermolysis bullosa in animals: a review

Construction and Analysis of Protein-Protein Interaction Network to Identify the Molecular Mechanism in Laryngeal Cancer

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