Corneal intraepithelial dyskeratosis is a rare condition, classically affecting American Haliwa-Saponi tribe members.

Herein, we present a new form of this disease in a Caucasian French family, and the way we identified its causative gene. The proband presented with severe bilateral corneal involvement, associated with palmoplantar and laryngeal localizations. Analyses of the cornea and the vocal cord showed the same histopathological characteristics.

Whole exome sequencing led to identify a novel missense mutation, M77T, for the gene NLRP1, which maps to chromosome 17p13.2. The variant followed the segregation in the family and was not found in extrafamilial control DNAs. We confirmed NLRP1 corneal expression and bioinformatical functional analysis showed that the amino acid change destabilized the protein structure and altered the protein function.

NLRP1 is known to be implicated in inflammation, autoimmune disorders, and cellular death. Our current results support plausible causality of this novel NLRP1 variant for a novel form of corneal intraepithelial dyskeratosis. (By Dr. Vincent Soler, http://jmg.bmj.com/content/early/2013/01/23/jmedgenet-2012-101325 )