111 Next generation sequencing is the suitable method for identification of hereditary dermatosis with EB symptom complex in Russian patients

Abstract

Epidermolysis bullosa (EB) is the umbrella term for a group of rare inherited skin fragility disorders caused by mutations in the different genes encoding structural proteins participating in the formation and functioning of dermoepidermal junction. Pathogenic genetic variants lead to polymorphic clinical phenotypes combined into 4 main types in accordance with the current nomenclature. 121 Russian children from 113 families aged 1 month to 17 year and 3 month, median 8 years with clinical manifestations of the EB symptom complex were selected for carrying out molecular genetic diagnostics. Next generation sequencing (NGS) was developed for identification of pathogenic variants in targeted regions of 24 genes. Diagnostic approach using NGS allowed to reveal 108 various mutant alleles. 57 variants were not described earlier. The most common form of epidermolysis bullosa is dystrophic, it was revealed in 77 (63,6%) children. EB simplex was detected in 35 (28,9%), EB junction was detected in 7 (5,8%) and the rarest Kindler syndrome was detected in 2 patients (1,7%) Missense mutation c.425A>G and splicing mutation c.682+1G>A in COL7A1 gene can be considered as major variants for Russian children with EB. In addition, we found that novel deletion c.3577del (p.A1193Lfs*72) revealed in homozygous state in 6 unrelated children living in Dagestan and 5 of them are representatives of the Dargwa ethnic group with high degree of traditionally consanguineous marriages. Pathogenic variants were found in all children which indicates that NGS can be used for identification of the etiological reasons of hereditary dermatosis with EB symptom complex successfully.