Epidermolysis Bullosa Simplex with Mottled Pigmentation and Migratory Circinate Erythema: Distinct Subtypes or a...

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) and migratory circinate erythema (EBS-MCE) are rare subtypes.
• These subtypes are typically associated with pathogenic variants in the KRT5 gene.

Purpose of the Study:

• To conduct a clinical and molecular analysis of patients with suspected EBS-MP or EBS-MCE in Argentina.
• To investigate the molecular epidemiology and genotype-phenotype correlations in a South American population.

Main Methods:

• Clinical and molecular analysis of 49 patients from 21 unrelated families.
• Genetic analysis to identify KRT5 and KRT14 variants, including a large KRT5 deletion.
• Tracing shared ancestry for a frequent KRT5 variant.

Main Results:

• Forty-eight out of 49 patients carried KRT5 variants; c.1649del was the most frequent, found in 44 patients from 16 families with shared ancestry.
• Clinical presentation included early-onset blistering, mottled pigmentation, nail dystrophy, and migratory erythema in 18 patients.
• Intrafamilial phenotypic variability was observed, suggesting modifier factors influence the disease spectrum.

Conclusions:

• This study provides the first molecular epidemiology report of EBS-MP in an undercharacterized South American population.
• Identified a common KRT5 variant and novel pathogenic variants, expanding the understanding of EBS-MP and EBS-MCE.
• Phenotypic variability underscores the dynamic nature of EBS-MP and EBS-MCE, influenced by genetic and potentially environmental factors.