A child presents with recurrent skin blistering at pressure points from birth, healed scars with milia formation, and nail dystrophy. Parents are consanguineous. Biopsy shows cleavage within the lamina lucida (sub-lamina lucida level). Electron microscopy shows hypoplastic hemidesmosomes with absent sub-basal dense plate. The gene mutation responsible for the most severe (lethal) form is:

• A COL7A1 (type VII collagen)
• B KRT5/KRT14 (keratin 5/14)
• C LAMA3/LAMB3/LAMC2 (laminin-332 subunits) — causing junctional EB Herlitz type ✓
• D PLEC (plectin)

Explanation

The sub-lamina lucida cleavage with hypoplastic/absent hemidesmosomes on EM is characteristic of junctional epidermolysis bullosa (JEB). The Herlitz (severe generalised) JEB type is caused by mutations in LAMA3, LAMB3, or LAMC2 encoding laminin-332 subunits — this form is lethal in infancy due to extensive skin/mucosal involvement, poor wound healing, and malnutrition. COL7A1 mutations cause dystrophic EB (sub-lamina densa cleavage). KRT5/KRT14 mutations cause simplex EB (intraepidermal, suprabasal cleavage). Plectin mutations cause EB with muscular dystrophy.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.