Molecular profiling of a cohort with epidermolysis bullosa in India: a single centre experience.

Background: Epidermolysis bullosa (EB) encompasses rare hereditary skin conditions marked by skin fragility, nail dystrophy and minor trauma-induced skin blisters.

Objectives: To identify genetic variants in patients with EB in India and to examine the relationship between genotypic and phenotypic manifestations.

Methods: Patients with EB seen consecutively over a period of 5 years at an outpatient department of dermatology (Postgraduate Institute of Medical Education and Research, Chandigarh, India) were included in the study. Baseline demographic data, birth history, family history, skin manifestations at birth, medical history, current cutaneous manifestations and the evolution of the disease were assessed and recorded. Genetic variants were identified using targeted gene panel sequencing for 23 EB-related genes and a genetic-phenotype analysis was performed.

Results: Our study included 65 patients with EB. Among these 65 patients with EB, 38 had dystrophic EB (DEB, 58%), 12 had junctional EB (JEB, 18%), 12 had EB simplex (EBS, 18%) and 3 had Kindler EB (KEB, 5%). Dominant and recessive forms of dystrophic EB accounted for 17% (n = 11) and 42% (n = 27), respectively, of the 65 individuals with EB. We identified 75 genetic variants, 59% (n = 44) newly discovered and 41% (n = 31) previously reported. Compound heterozygous variants were more frequent (56%; 15/27) than homozygous ones (44%; 12/27) in individuals with recessive DEB. Patients with JEB harboured LAMB3 mutations more frequently, whereas patients with EBS harboured KRT5 and KRT14 missense heterozygous mutations. Patients with KEB had homozygous mutations in FERTM1.

Conclusions: Our study has unveiled several novel genetic variants and severe phenotypes associated with nonsense genetic variants. These findings offer valuable insights for future clinical assessments and tailored management strategies.