Gene therapy for keratin genodermatoses: striving forward but obstacles persist.

D'Alessandro and colleagues have investigated stress responses in keratinocyte cell lines lacking keratin 14 (K14-null mutation). In this issue, they describe the use of this model to assess the extent of phenotypic rescue achievable by wild-type K14 in the absence of a dominant negative mutation. This work provides proof that, in principle, transfection of wild-type K14 on a null background can significantly normalize the cell and reduce stress responses.

Peeling skin syndrome: genetic defects in late terminal differentiation of the epidermis.

In this issue, Israeli and colleagues confirm that homozygous mutations in corneodesmosin (CDSN) cause type B peeling skin syndrome (PSS), an autosomal recessive skin disorder. The deletion mutation described resulted in a frameshift, producing a downstream premature stop codon and early truncation of the protein. The recently described CDSN nonsense mutation in another PSS family also resulted in protein truncation and nonsense-mediated mRNA decay.

Defining the complex epithelia that comprise the canine claw with molecular markers of differentiation.

Canine claws are complex epithelial structures resembling the mammalian hair fibre, and human nail plate, in terms of tissue-specific differentiation. They are composed of several distinct epithelial cell lineages undergoing either hard or soft keratinization. The claw plate has three distinct regions: stratum externum, stratum medium (SM) and stratum internum and the underside and tip are cushioned by a soft keratinizing epithelium, the sole.

Mutations in a keratin 6 isomer (K6c) cause a type of focal palmoplantar keratoderma.

Twenty years have elapsed since keratin mutations were linked to cutaneous genodermatoses, and we now know that they cause 40 different genetic disorders. In this issue, Wilson et al. have identified KRT6C mutations in patients with focal palmoplantar keratoderma (FPPK), but debate concerning overlapping phenotypes between FPPK and pachyonychia congenita (PC) will continue because only one family has nail involvement.

A novel mutation (p.Thr198Ser) in the 1A helix of keratin 5 causes the localized variant of epidermolysis bullosa simplex.

A novel missense mutation (p.Thr198Ser) in the 1A helix of keratin 5 (K5) has been identified in a four-generation family with a history of the localized variant of epidermolysis bullosa simplex (EBS-loc), a genetic skin fragility disorder caused by K5 or K14 mutations. Genomic DNA was isolated from blood samples of patients and their healthy relatives, and all exons of the genes encoding K5 and K14 (KRT5 and KRT14) were amplified by PCR and directly sequenced.

New consensus nomenclature for mammalian keratins.

Keratins are intermediate filament-forming proteins that provide mechanical support and fulfill a variety of additional functions in epithelial cells. In 1982, a nomenclature was devised to name the keratin proteins that were known at that point. The systematic sequencing of the human genome in recent years uncovered the existence of several novel keratin genes and their encoded proteins.

Numerous keratinocyte subtypes involved in wound re-epithelialization.

The expression of different keratin intermediate filaments has been used to define keratinocyte maturation and different phenotypic subtypes involved in acute wound (AW) healing. Immunohistochemistry with specific anti-keratin monoclonal and polyclonal antibodies was used to examine AW in normal healthy volunteers (n = 16). In all wounds examined, basal keratinocytes and cells at the leading edge of the wound expressed keratins K5 and K14.

Splice site and deletion mutations in keratin (KRT1 and KRT10) genes: unusual phenotypic alterations in Scandinavian patients with epidermolytic hyperkeratosis.

Epidermolytic hyperkeratosis is a rare autosomal dominant inherited skin disorder caused by keratin 1 or keratin 10 mutations. Keratins are major structural proteins of the epidermis, and in keratinocytes committed to terminal differentiation the intermediate filaments are composed of keratin 1 and keratin 10 heterodimers. The majority of reported mutations (86.