Pachyonychia congenita (PC) is a group of autosomal dominant disorders characterized by dystrophic nails and other ectodermal aberrations. A gene for Jackson-Lawler PC was recently mapped to the type I keratin cluster on 17q. Here, we show that a heterozygous missense mutation in the helix initiation motif of K17 (Asn92Asp) co-segregates with the disease in this kindred. We also show that Jadassohn-Lewandowsky PC is caused by a heterozygous missense mutation in the helix initiation peptide of K16 (Leu130Pro). The known expression patterns of these keratins in epidermal structures correlates with the specific abnormalities observed in each form of PC.

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Infection with herpes simplex virus (HSV) is a common worldwide problem. Primary infection with HSV-1 rarely causes significant problems although widespread involvement in atopic eczema can be life-threatening as may associated encephalitis. Keratoconjunctivitis, pharyngitis and hepatitis can also complicate primary infection. Twenty to 40% of the population at some stage have recurrent orolabial infections with HSV although in only 1% of these cases is this recurrence severe. Recurrent erythema multiforme appears to be associated with HSV-65% of patients are thought to have preceding herpes labialis. Many primary and recurrent infections with HSV-1 require little more than topical antiseptic therapy to control secondary infection. Systemic acyclovir, however, is indicated in various situations including complicated primary infection, infection in neonates, eczema herpeticum, HSV infections in the immunocompromised, and recurrent erythema multiforme. In the latter, prophylactic treatment with 6 months acyclovir appears to be effective.

We and others have previously shown that ichthyosis bullosa of Siemens, an autosomal dominant disorder characterized by epidermal thickening and blistering, is caused by mutations in the late-differentiation keratin K2e. Here, we have determined the genomic organization and complete sequence of the KRT2E gene, which consists of nine exons, spanning 7634 bp of DNA. The gene was mapped by high-resolution radiation-hybrid mapping to the interval between microsatellite markers D12S368 and CHLC.GATA11B02.1112. Several intragenic polymorphisms were detected, including an 18 bp duplication in exon 1, corresponding to the V1 domain of the K2e polypeptide. Genomic polymerase chain reaction conditions were optimized for all exons, and two novel mutations, N192Y in the 1A domain and E482K in the 2B domain of K2e, were found in ichthyosis bullosa of Siemens families. Mutations were excluded from 50 normal unrelated individuals by restriction analysis. These results emphasize that mutations in K2e underlie ichthyosis bullosa of Siemens and provide a comprehensive mutation detection strategy for ongoing studies of keratinizing disorders.