Targeted NGS in Diagnostics of Genodermatosis Characterized by the Epidermolysis Bullosa Symptom Complex in 268 Russian Children

Abstract

The pathogenic variants of genes encoding proteins, participating in the formation and functioning of epidermis and dermo-epidermal junctions, create a large variety of clinical phenotypes from: small localized to severe generalized dermatitis, as well as early, or even, prenatal death due to extensive epidermis loss. The diagnostic panel in this study was developed for the purposes of identifying these pathogenic genetic variants in 268 Russian children, who possessed the epidermolysis bullosa symptom complex in a selection of 247 families. This panel included the targeted areas of 33 genes, which are genetic variants that can lead to the development of the phenotype mentioned above. The usage of next generation sequencing allowed the revelation of 192 various altered alleles (of which 109 alleles were novel, i.e., had not been described previously). In addition, it allowed the definition of the genetic variants that are both typical for most of the examined children and for the separate ethnic groups inhabiting modern Russia. We found that the most characteristic mutations for the Dargin and Chechen ethnic groups are the c.3577del deletion in the COL7A1 gene and the c.2488G>A missense mutation in the COL17A1 gene, respectively. In addition, the study of haplotypes of microsatellite markers, which we managed to conduct in the Dargin population, confirmed the presence of the founder effect.

Keywords: children; epidermolysis bullosa; founder effect; microsatellite markers; next generation sequencing.

Figure 1

The incidence expressed as percentage cases of different dermatosis forms with the EB symptom complex in examined Russian children.

Figure 2

Variety of genes and the proportion of mutations in 247 examined families with the EB phenotype.

Figure 3

The frequencies and spectrum of COL7A1 gene mutations detected more than twice in Russian children with dystrophic EB.

Figure 4

The frequencies and spectrum of detected mutations in the KRT14 gene in Russian children with an EB phenotype.

Figure 5

The frequencies and spectrum of detected mutations in the KRT5 gene in Russian children with EB simplex.

Figure 6

The frequencies and spectrum of detected mutations in the COL17A1 gene in Russian children with junctional EB.