Novel autosomal dominant mutation in loricrin presenting as prominent ichthyosis

DEAR EDITOR, Loricrin keratoderma (syn. Camisa syndrome, OMIM 604117) is a rare autosomal dominant genodermatosis characterized by palmoplantar keratoderma and ichthyosis. It is caused by mutations in loricrin, a small basic protein synthesized in the upper granular layer, which becomes a major constituent of the cornified cell envelope. Seven distinct mutations in loricrin have been reported in 15 unrelated pedigrees to date. We report a multi-generation family with prominent ichthyosis and palmoplantar involvement due to a novel mutation in loricrin. The proband was a 14-year-old boy who presented with generalized dryness and scaling affecting his trunk and all four limbs, previously thought to be ichthyosis vulgaris, which was reported from early childhood (Fig. 1a). Clinical examination revealed widespread, prominent ichthyosis and mild diffuse transgredient hyperkeratosis of palms and soles. There was no evidence of atopic dermatitis or keratosis pilaris. His mother and eight other family members were similarly affected (Fig. 1b). Subsequently, a further child was born with a collodion membrane followed by generalized ichthyosis. Biopsies of affected skin were processed for light and electron microscopy by standard methods (upper back of the proband’s mother) or for electron microscopy only (affected acral skin from the proband’s grandfather). Following informed consent, genomic DNA was extracted from blood or saliva samples from 10 affected and unaffected family members (Fig. 1a). A whole exome sequencing approach was taken to analyse the proband’s DNA (Methods S1; see Supporting Information).