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Molecular confirmation of the unique phenotype of epidermolysis bullosa simplex with mottled pigmentation
Author(s) -
Irvine A.D.,
Rugg E.L.,
Lane E.B.,
Hoare S.,
Peret C.,
Hughes A.E.,
Heagerty A.H.
Publication year - 2001
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2001.03950.x
Subject(s) - epidermolysis bullosa simplex , epidermolysis bullosa , mutation , phenotype , point mutation , dermatology , keratin 5 , pathology , palmoplantar keratoderma , keratoderma , biology , medicine , genetics , keratin , hyperkeratosis , gene
Background A distinctive subtype of epidermolysis bullosa simplex, with the additional feature of mottled pigmentation (EBS–MP), was initially characterized in a Swedish family in 1979, and seven further families have been reported. Features of EBS–MP that are observed in most affected patients include acral blistering early in childhood, mottled pigmentation distributed in a number of sites, focal punctate hyperkeratoses of the palms and soles, and dystrophic, thickened nails. The genetic basis of EBS–MP has been ascribed in five unrelated families to a heterozygous point mutation, P25L, in the non‐helical V1 domain of K5. Objectives We report a clinical, ultrastructural and molecular study of two of the earliest families to be clinically characterized as EBS–MP. Methods The P25L mutation was identified in all affected members of each of these families, bringing the total number of EBS–MP families with this mutation to seven. Results This unusual recurrent mutation may uniquely cause EBS–MP. Conclusions While the exact molecular mechanisms by which this mutation causes epidermolysis, palmoplantar keratoderma and pigmentation remain elusive, we suggest possible molecular mechanisms through which the P25L substitution could cause this unusual phenotype.