Abstract
Ichthyosis is a genetically heterogeneous genodermatosis characterized by severely rough, dry and scaly skin. We report two consanguineous families with congenital ichthyosis. Combined positional mapping and exome sequencing of the two families revealed novel homozygous likely deleterious variants in
PRSS8
(encoding prostasin) within a linkage locus on chromosome 16. One variant involved a canonical splice site and was associated with reduced abundance of the normal transcript, while the other was a missense variant that altered a highly conserved residue. The phenotype of
Prss8
knockout mouse bears a striking resemblance to the one we describe in human patients, including the skin histopathology. Our data suggest a novel
PRSS8
-related ichthyosis disorder.