Synonymous COL7A1 c.6846G>C in Dystrophic Epidermolysis Bullosa: Oral Phenotypic Expansion and Palatal Ultrastructure

Abstract

Background Dystrophic epidermolysis bullosa (DEB) results from pathogenic COL7A1 variants that impair collagen VII–dependent epithelial anchorage. Hard-palatal papules, absent lingual frenula, and ultrastructural characterization of these lesions have not been reported. Case description Three siblings born to consanguineous, clinically unaffected Thai-Muslim parents developed DEB characterized by trauma-induced blistering, scarring, pigmentation, and nail dystrophy. All three also had absent lingual frenula and recurrent hard-palatal papules that coalesced into keratinized, cobblestone-like plaques. Histopathology showed epithelial–connective tissue separation with epithelial hyperplasia, inflammation, and fibrosis. Transmission electron microscopy demonstrated subepithelial cleavage, with basal keratinocytes retained on the epithelial side and lamina propria forming the blister floor. Whole-exome sequencing identified homozygous COL7A1 c.6846G>C (p.Leu2282Leu) in affected siblings; unaffected parents were heterozygous. This synonymous variant previously caused autosomal dominant DEB pruriginosa through exon 87 skipping. Conclusions and practical implications This report identifies previously unrecognized palatal plaques and provides the first ultrastructural characterization of these lesions in COL7A1 -associated DEB. The same COL7A1 variant may show dominant expression in some families and recessive-like expression in others. Their recurrent blistering and subepithelial cleavage strongly support an association with DEB. Absent lingual frenula remain an unconfirmed finding requiring further study.