A severe familial phenotype of Ichthyosis Curth-Macklin caused by a novel mutation in theKRT1gene

Abstract

Funding sources: This study was supported by the Universidad del Rosario, Grant CS/Genetics 2012. Conflicts of interest: none declared. Madam, Ichthyosis Curth–Macklin (ICM; Mendelian Inheritance in Man database #146590) is a rare genetic disorder that is clinically characterized by severe palmoplantar keratoderma. The skin of patients with ICM is characterized by extensive dark spiky or verrucous plaques that affect the large joints and the trunk. In some cases these lesions can cover the entire body. Differentiating keratinocytes of ICM tissues display ultrastructural anomalies such as keratin intermediate filaments (KIF), aggregation into peripheral shells, perinuclear vacuolization and binucleated cell formation.1 ICM, as well as other keratinopathic ichthyoses, is caused by mutations of the keratin 1 gene (KRT1) that lead to an impairment of the KIF network assembly in the cytoplasm of keratinocytes.2 At the protein level, these mutations are located in the variable (V2) domain of the protein.1, 3, 4 In this study, we report two related women of Colombian origin, affected by a severe ICM phenotype, who present a novel KRT1 mutation. These patients attended the Dermatology Unit of the Carlos Ardila Lulle Clinic of Bucaramanga (Colombia). This study has been approved by the Ethical Committee at Universidad del Rosario and was conducted according to the Declaration of Helsinki principles. The index case (IC) provided a consent form to participate in the study and signed it on behalf of her daughter.