First Report of Homozygous <i>COL7A1</i> c.5756delG Mutation Causing Recessive Dystrophic Epidermolysis Bullosa in a Non‐Consanguineous Japanese Family

ABSTRACT Severe recessive dystrophic epidermolysis bullosa (RDEB) is usually caused by biallelic loss‐of‐function mutations in COL7A1 . While the c.5756delG variant has been previously reported in heterozygous form, its clinical impact in homozygosity has not been described. We report a Japanese male infant born to non‐consanguineous parents who presented at birth with generalized blistering and erosions. Skin biopsy revealed sub‐lamina densa blistering with absence of anchoring fibrils, and immunofluorescence showed complete loss of type VII collagen. Whole‐exome sequencing identified a homozygous COL7A1 c.5756delG deletion, confirmed by carrier status in both parents. RNA analysis demonstrated no exon skipping, confirming a frameshift and premature termination codon. This is the first report of homozygous COL7A1 c.5756delG causing RDEB. This case not only adds a novel homozygous COL7A1 mutation to the mutational spectrum of RDEB but also emphasizes the importance of zygosity and functional validation in interpreting the clinical impact of COL7A1 variants.