Advantages of whole-exome sequencing over immunomapping in 67 Brazilian patients with Epidermolysis bullosa

Abstract

Background: Epidermolysis bullosa (EB) is characterized by skin fragility and blistering. In Brazil, the diagnosis is usually obtained through immunomapping, which involve skin biopsy procedures. Most recently, Whole Exome Sequencing (WES) has become an important tool for the diagnosis of the subtypes of EB, providing information on prognosis as well as allowing appropriate genetic counseling for the families. Objective: To compare the results of immunomapping and molecular analysis and to describe the characteristics of a Brazilian cohort of patients with EB. Methods: Patients were submitted to clinical evaluation and WES using peripheral blood samples. WES results were compared to those obtained from immunomapping testing by skin biopsy. Results: 67 patients from 60 families were classified: 47 patients with recessive dystrophic EB (DEB), 4 with dominant DEB, 15 with EB simplex (EBS) and 1 with junctional EB (JEB). Novel causative variants were: 10/60 (16%) in COL7A1associated with recessive DEB and 3 other variants in dominant DEB; one homozygous variant in KRT5 and another homozygous variant in PLEC, both associated with EBS. Immunomapping was available for 59 of the 67 patients and the result was concordant with exome results in 37 (62%), discordant in 13 (22%) and inconclusive in 9 patients (15%). Conclusion: Although immunomapping has been useful in services where molecular studies are not available, this invasive method may provide a misdiagnosis or an inconclusive result in more than 1/3 of the patients. This study shows that WES is an effective method to the diagnosis and genetic counseling of EB patients.