Gene panel for the diagnosis of epidermolysis bullosa: proposal for a viable and efficient approach

Abstract

Background Epidermolysis bullosa is characterized by cutaneous fragility and blistering. Historically, diagnosis is achieved by immunofluorescence mapping or transmission electron microscopy, both involving biopsy procedures. Genetic analysis, especially through next-generation sequencing, is an important tool for the diagnosis of this disease. In Brazil, access to diagnostic methods is limited, and consequently, most patients do not have an accurate diagnosis. Diagnosis allows the indication of prognosis and genetic counselling of the patient. Objectives To evaluate the cost-effectiveness of a gene panel compared to immunofluorescence mapping and transmission electron microscopy by analyzing its benefits, limitations, and economic aspects. Methods The gene panel included the 11 main genes associated with epidermolysis bullosa. The techniques were compared, assessing the average cost, advantages, and limitations, through a price survey and literature review. Results Both immunofluorescence mapping and transmission electron microscopy require skin biopsy, are dependent on the investigator’s expertise, and are subject to frequent inconclusive results. The gene panel is effective for the conclusive diagnosis of epidermolysis bullosa, presents high efficiency and accuracy, is economically feasible, and excludes the need for biopsy. The gene panel allows for prognosis, prenatal genetic diagnosis, and genetic counseling. Study limitations It was not possible to find laboratories that perform transmission electron microscopy for epidermolysis bullosa diagnosis in Brazil. Conclusion This study supports the gene panel as the first-choice method for epidermolysis bullosa diagnosis.

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

“…Despite being considered more expensive than immunomapping at rst, it is important to express that NGS costs keep constantly falling over the last years. As a matter of fact, the potential cost-effectiveness of NGS panel focused in genes related with EB for diagnosis in a country with continental dimensions such as Brazil has already been suggested by another recent study 7 . Even though our study used wholeexome sequencing (WES) for genetic analysis, we believe these results are generalizable to NGS techniques.…”

“…In this scenario, molecular analysis has become an important tool towards a more precise diagnosis of EB, especially given the recent consolidation and expansion of NGS techniques 4,5,6,7,8 . Unsurprisingly, its use has been strongly recommended not only due to its precision and potential lesser cost, but also because it would avoid the harm of damaging the skin in such vulnerable patients, since it works ne with just one drop of blood or even a spit of saliva from the patient.…”