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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

Oxidative stress and mitochondrial dysfunction in Kindler syndrome

Authors: Elisabeth Zapatero-Solana, Jose Luis García-Giménez, Sara Guerrero-Aspizua, Marta García, Agustí Toll, Eulalia Baselga, Maria Durán-Moreno, Jelena Markovic, Jose Manuel García-Verdugo, Claudio J Conti, Cristina Has, Fernando Larcher, Federico V Pallardó, Marcela Del Rio

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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Abstract

Background

Kindler Syndrome (KS) is an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, premature aging, and propensity to skin cancer. In spite of the knowledge underlying cause of this disease involving mutations of FERMT1 (fermitin family member 1), and efforts to characterize genotype-phenotype correlations, the clinical variability of this genodermatosis is still poorly understood. In addition, several pathognomonic features of KS, not related to skin fragility such as aging, inflammation and cancer predisposition have been strongly associated with oxidative stress. Alterations of the cellular redox status have not been previously studied in KS. Here we explored the role of oxidative stress in the pathogenesis of this rare cutaneous disease.

Methods

Patient-derived keratinocytes and their respective controls were cultured and classified according to their different mutations by PCR and western blot, the oxidative stress biomarkers were analyzed by spectrophotometry and qPCR and additionally redox biosensors experiments were also performed. The mitochondrial structure and functionality were analyzed by confocal microscopy and electron microscopy.

Results

Patient-derived keratinocytes showed altered levels of several oxidative stress biomarkers including MDA (malondialdehyde), GSSG/GSH ratio (oxidized and reduced glutathione) and GCL (gamma-glutamyl cysteine ligase) subunits. Electron microscopy analysis of both, KS skin biopsies and keratinocytes showed marked morphological mitochondrial abnormalities. Consistently, confocal microscopy studies of mitochondrial fluorescent probes confirmed the mitochondrial derangement. Imbalance of oxidative stress biomarkers together with abnormalities in the mitochondrial network and function are consistent with a pro-oxidant state.

Conclusions

This is the first study to describe mitochondrial dysfunction and oxidative stress involvement in KS.
Appendix
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Metadata
Title
Oxidative stress and mitochondrial dysfunction in Kindler syndrome
Authors
Elisabeth Zapatero-Solana
Jose Luis García-Giménez
Sara Guerrero-Aspizua
Marta García
Agustí Toll
Eulalia Baselga
Maria Durán-Moreno
Jelena Markovic
Jose Manuel García-Verdugo
Claudio J Conti
Cristina Has
Fernando Larcher
Federico V Pallardó
Marcela Del Rio
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-014-0211-8

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