COL7A1 – Pretibial Dystrophic Epidermolysis Bullosa

Pretibial dystrophic epidermolysis bullosa (Pretibial dystrophic epidermolysis bullosa) is a rare localized subtype of dystrophic epidermolysis bullosa characterized by trauma-induced blisters and scarring predominantly on the lower legs. It is caused by mutations in the type VII collagen gene COL7A1 that impair procollagen VII processing and anchoring fibril formation (PMID:10583163).

Genetic studies indicate both autosomal recessive and autosomal dominant inheritance. A recessive case in a 33-year-old man carried a 14-bp deletion at the exon 115 splice donor site, causing in-frame exon skipping and accumulation of unprocessed procollagen VII at the dermal–epidermal junction (PMID:10583163).

Late-onset recessive PEB was documented in a patient presenting in his fifth decade with compound heterozygous mutations c.3840del (p.Gly1281AlafsTer?) and c.8371C>T (p.Arg2791Trp), underscoring the variable age of onset and the importance of molecular screening (PMID:23786535).

A glycine substitution mutation c.7867G>T (p.Gly2623Cys) segregated in a five-generation pedigree with a LOD score of 3.61 at θ=0, confirming autosomal dominant PEB in Taiwanese kindreds (PMID:8541842).

An 18-bp deletion c.6849_6867del (p.Gly2284GlufsTer?) was identified in an Italian family across three generations, producing shortened collagen VII polypeptides and a mild, localized pretibial blistering phenotype (PMID:32840914).

Functional assays—including immunofluorescence with NC-2 domain-specific antibodies and electron microscopy—demonstrate markedly reduced mature collagen VII and hypoplastic anchoring fibrils, consistent with a haploinsufficiency mechanism in PEB (PMID:10583163).

Together, segregation data, multiple probands with distinct COL7A1 alleles, and concordant functional studies support a moderate clinical validity for the COL7A1–PEB association. Key take-home: COL7A1 mutational analysis is essential for definitive diagnosis, genetic counseling, and guiding future therapeutic strategies in pretibial dystrophic epidermolysis bullosa.

References

• British Journal of Dermatology • 1999 • Pretibial dystrophic epidermolysis bullosa: a recessively inherited COL7A1 splice site mutation affecting procollagen VII processing. PMID:10583163
• Clinical and Experimental Dermatology • 2013 • Late-onset pretibial recessive dystrophic epidermolysis bullosa. PMID:23786535
• Human Molecular Genetics • 1995 • Pretibial epidermolysis bullosa: genetic linkage to COL7A1 and identification of a glycine-to-cysteine substitution in the triple-helical domain of type VII collagen. PMID:8541842
• Pediatric Dermatology • 2020 • Dominant pretibial dystrophic epidermolysis bullosa in an Italian family. PMID:32840914

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