A usual frameshift and delayed termination codon mutation in keratin 5 causes a novel type of epidermolysis bullosa simplex with migratory circinate erythema

Journal of Drugs in Dermatology, Dec, 2003

Gu LH, Kim SC, Ichiki Y, Park J, Nagai M, Kitajima Y. J Invest Dermatol 2003 Sep: 121(3):482-5.

The authors report a unique familial type of epidermolysis bullosa simplex (EBS) and a novel mutation in the keratin gene KRT5, i.e., a frameshift and delayed stop codon inconsistent with any subtype described before. The main pathological findings were migratory circinate erythema and multiple vesicles on the circular belt-like areas affected by erythema. Microscopic studies via electron microscopy (EM) of skin biopsies showed a reduction in the number of keratin intermediate filaments in the basal cells without tonofilament clumping. The deletion in the KRT 5 gene (deletion of guanine at 1649) is predicted to produce a mutant keratin 5 protein with a frameshift of its terminal 41 amino acids and 35 amino acids longer than the wild-type keratin 5 protein due to a delayed termination codon. The by-product was an abnormal elongated keratin protein that most likely leads to an atypical clinical phenotype that has never been reported, possibly by interfering with the functional interaction between keratin and its associated proteins. All in all, this mutation has not been previously described, and the interference of keratin and its proteins produces EBS with a migratory circinate erythema.

JDD ARTICLE EVALUATION

Mutations for KRT-5 have been documented for EBS in types Dowling-Meara (DM), Weber-Cockayne (WC), and Koebner (K), but most are in the V1 region; none had mutations in the V2 domain of K5. As a result of this of this K5 mutation in V2 we have a less severe form of EBS-DM, but this new fore1 of EBS presents with a different age of onset (birth vs. childhood), generalized vesicles (DM) vs. localized, and annular erythematous vesicles. There ate no hyperkeratoses of the palms and soles, no nail changes, and no pyloric atresia. Because this entity presents with none of the clinical findings of EBS-DM, it is on the V2 region of KS, and there is no clumping of tonofilaments nor herpetiform vesicles, we should consider a new type of EBS in our classification. The authors suggest EBS with migratory circinate erythema (MCE): I would recommend EBS-GuKim type (EHS-GK). In summary, a new type of riBS has been identified, similar to EBS-DM in genetics but unique in clinical presentation and microscopy. presenting with a migratory cireinam erythema.