Ophthalmic phenotype associated with a novel mutation in LAMB3 gene linked to uncommon Intermediate Junctional...

Intermediate Junctional Epidermolysis Bullosa (JEB) is an extremely rare condition, with an incidence of slightly more than two per million live births. Patients with Epidermolysis Bullosa are classified using the "onion skinning" approach, which includes the major EB type, phenotypic characteristics, inheritance mode, targeted protein and its skin expression, gene involved, mutation types, and specific mutation(s) and location. This facilitates recognition of syndromic EB and aids in genetic counseling.

To report a patient with Intermediate JEB, perform a detailed ophthalmic evaluation, and identify the genetic cause through testing.

A 13-year-old girl presented with recurrent epithelial erosions since 2015, with minimal or no trauma. Ophthalmic exam revealed bilateral faint corneal opacities and prominent corneal innervation. Systemic findings included hypodontia and hypopigmentation of the forearms and retroauricular region. Whole exome sequencing revealed a homozygous c.2137+2T > G variant in the LAMB3 gene, likely disrupting mRNA splicing by altering the donor splice site. This mutation is expected to cause a frameshift and dysfunctional protein product. It was confirmed by Sanger sequencing.

The ocular, dental, and dermal findings support a diagnosis of EB, highlighting the importance of multidisciplinary evaluation. Identification of this novel LAMB3 variant expands the known genotypic spectrum of JEB and enhances understanding of its molecular basis. This contributes to accurate diagnosis and improved genetic counseling for affected families.