Novel and recurrent mutations in the 1B domain of keratin 1 in palmoplantar keratoderma with tonotubules

Abstract

Conflicts of interest: none declared. Palmoplantar keratodermas (PPKs) are a large group of disorders characterized by hyperkeratosis of palms and soles. They can be classified by their mode of inheritance, the morphology and distribution of the hyperkeratosis (diffuse, focal or punctate), the involvement of other ectodermal structures, the presence or absence of associated nonectodermal features and the morphological findings at light and electron microscopic levels.1 Mutations in a variety of proteins are associated with different types of PPK. These proteins include keratins, proteins of the cornified cell envelope (loricrin), and molecules for cohesion (desmoglein, desmoplakin), intercellular communication (connexins) and transmembrane transduction (cathepsin C). PKK of Voerner is the most frequently inherited PPK.2 It is transmitted in an autosomal dominant mode and starts within the first year of life. It is characterized by a diffuse, yellowish or erythematous hyperkeratosis, sometimes covering bullous lesions, that is sharply demarcated with an erythematous margin; typically there is no progression to the dorsal aspects of hands and feet. Additional features frequently seen are knuckle pad‐like keratoses over the flexural areas of the finger joints, clubbing of the nails, and hyperhidrosis.3 Mutations in the keratin 9 gene (KRT9) have been identified in this PPK.3