ABSTRACT
Epidermolysis bullosa simplex is a heterogeneous group of inherited bullous disorders due to mutations in keratins 5 and 14. We report two different mutations in keratin 14 at codon 119 of the helix initiation peptide, each with different phenotypic expression. One, a sporadic case that clinically resembles Dowling-Meara epidermolysis bullosa simplex, resulted from conversion of methionine to threonine (M119T). The other, a multigeneration family with the Koebner phenotype, resulted from a previously unreported methionine to valine substitution (M119V). We suggest that loss of hydrophobicity during conversion of methionine to threonine is responsible for the more severe presentation of the first family, whereas maintenance of the hydrophobic nature of the amino acid with conversion to valine resulted in a less severe variant of epidermolysis bullosa simplex. Although most prior mutations in the highly conserved boundary motif of the alpha-helix have resulted in the Dowling-Meara subtype, our findings confirm that it is not always possible to predict the epidermolysis bullosa simplex severity on the basis of the location of the mutation along the keratin polypeptide. The specific amino acid substitution may be more critical in some cases.
Subject(s)
Codon , Epidermolysis Bullosa Simplex/genetics , Keratins/genetics , Point Mutation/genetics , Adolescent , Base Sequence/genetics , Child , Epidermolysis Bullosa Simplex/pathology , Female , Humans , Keratin-14 , Male , Molecular Sequence Data , Pedigree , Phenotype , Protein Structure, SecondaryABSTRACT
Metastatic Crohn's disease (MCD) is a rare extraintestinal manifestation of Crohn's disease characterized by the histologic finding of granulomatous dermatitis at a site noncontiguous to the gastrointestinal tract. An adolescent had MCD of the face that was initially mistaken for severe, treatment-resistant acne. Histopathologic and microbiologic evaluation, combined with clinical examination and response to therapy, ultimately led to the correct diagnosis. Mycobacterium paratuberculosis is a suspected cause of Crohn's disease. Polymerase chain reaction was used to detect genomic DNA specific for the organism in biopsy specimens from the patient's cutaneous lesions. This study failed to demonstrate M. paratuberculosis in the specimens.
