The P25L mutation in the KRT5 gene in a Japanese family with epidermolysis bullosa simplex with mottled pigmentation.

Abstract

Sir, Epidermolysis bullosa simplex (EBS) with mottled pigmentation (EBS‐MP; OMIM 131960) is an autosomal dominant disorder characterized by acral intraepidermal blisters after minor trauma, mottled pigmentation on the trunk and extremities, punctuate palmoplantar hyperkeratoses, and nail dystrophy.1, 2 Histologically, basal keratinocyte degeneration and the basal cell layer level of splitting are similar to those seen in other subtypes of EBS. By electron microscopic examination, areas of vacuolization are seen adjacent to the nucleus, and atypical clumped keratin intermediate filaments are also demonstrated. Within a hyperpigmented lesion, basal keratinocytes contain abundant mature melanosomes. These are also observed within dermal melanophages and the cytoplasm of Schwann cells.1, 3 Keratin 5 (K5) and Keratin 14 (K14) are known to be essential for the basal keratinocyte cytoskeleton and are defective in several forms of EBS. Recently, the genetic basis of EBS‐MP has been reported in seven unrelated families of European origin to a heterozygous missense mutation: P25L in the nonhelical V1 domain of K5.3–6 This recurrent mutation may uniquely cause the EBS‐MP phenotype and suggests additional roles for keratin intermediate filaments, such as melanosome transportation. We report a Japanese family with two members affected with EBS‐MP. Analysis of the KRT5 gene also showed the P25L mutation.