Epidermolysis bullosa simplex: genotype-phenotype correlations

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Abstract

Epidermolysis bullosa simplex (EBS) includes a group of diseases characterized by varying severity, possible damage to visceral organs, and various outcomes ranging from complete regression of the rash to death. The initial clinical manifestations of EBS do not allow for predicting further course of the disease, however clinical and genetic correlations may be used for this purpose. We analyzed the literature from the PubMed and RSCI databases to characterize the clinical and genetic correlations in EBS. The analysis revealed that the most severe course of skin lesions in patients with EBS is associated with mutations in the KRT5 and KRT14 genes which alter the HIP (helix initiation peptide) and HTP (helix termination peptide) motifs in the corresponding proteins as well as the helical regions of keratins 5 and 14. The study also identified factors that can reduce reliability of predicting the course of EBS using clinical and genetic correlations. These include the degree of difference in the physical and chemical properties of the mutant and wild-type amino acids in case of missense mutations as well as the possible influence of other gene variants that may contribute to the clinical presentation of the disease. Detection of PLEC1 gene mutations suggests the possibility of developing muscular dystrophy, KLHL24 cardiomyopathy, CD151 nephropathy and deafness over the course of an EBS patient’s life. Thus, clinical and genetic correlations have been established that can be used to predict the course of EBS, and limitations for their application have been determined.

About the authors

Vadim V. Chikin

State Research Center of Dermatovenereology and Cosmetology

Email: chikin@cnikvi.ru
ORCID iD: 0000-0002-9688-2727
SPIN-code: 3385-4723

MD, Dr. Sci. (Med.), Senior Research Associate

Russian Federation, Moscow

Arfenia E. Karamova

State Research Center of Dermatovenereology and Cosmetology

Author for correspondence.
Email: karamova@cnikvi.ru
ORCID iD: 0000-0003-3805-8489
SPIN-code: 3604-6491

MD, Cand. Sci. (Med.), Assistant Professor

Russian Federation, Moscow

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