PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Ichthyosis is a group of genetic skin disorders causing dry, scaly skin.
• Congenital ichthyosis presents at birth and has various genetic causes.
• Understanding the genetic underpinnings of ichthyosis is crucial for diagnosis and potential treatments.

Purpose of the Study:

• To investigate the genetic cause of congenital ichthyosis in two consanguineous families.
• To identify novel genes and variants associated with this genodermatosis.
• To explore the role of the PRSS8 gene in ichthyosis pathogenesis.

Main Methods:

• Combined positional mapping and exome sequencing were utilized.
• Analysis focused on identifying homozygous variants within a specific chromosomal linkage locus.
• Phenotypic correlation was assessed using a Prss8 knockout mouse model.

Main Results:

• Novel homozygous likely deleterious variants in the PRSS8 gene (encoding prostasin) were identified.
• One variant affected a splice site, leading to reduced normal transcript levels.
• A missense variant in PRSS8 altered a highly conserved residue.
• Prss8 knockout mice exhibited a phenotype similar to the affected human patients.

Conclusions:

• A novel PRSS8-related ichthyosis disorder has been identified.
• Mutations in PRSS8 are implicated as a cause of congenital ichthyosis.
• This finding expands the known genetic heterogeneity of ichthyosis.