KLICK Syndrome via the POMP Gene

KLICK syndrome is a rare skin disorder characterized by Keratosis Linearis with Ichthyosis Congenita and sclerosing Keratoderma. The major features include congenital ichthyosis and palmoplantar keratoderma hyperkeratosis (Vahlquist et al. 1997).

Pathogenic variants in the POMP gene cause autosomal recessive KLICK syndrome. POMP (proteasome maturation protein) is a key component for 20S proteasome formation. To date, one small homozygous deletion (c.-95delC) in the pre-coding region of the POMP gene was found in 12 KLICK syndrome patients from 8 unrelated European families (Dahlqvist et al. 2010). Also, a small heterozygous duplication (c.340_344dupTTTGA, p.Glu115Aspfs*20) was found in one patient affected with CANDLE disease, an autosomal dominant immune-dysregulatory disease characterized by chronic atypical neutrophilic dermatosis with lipodystrophy and elevated Temperature (Brehm et al. 2015).

A recurrent pathogenic variant in the POMP gene was found in 12 KLICK syndrome patients from 8 unrelated European families (Dahlqvist et al. 2010). However, due to limited publications, the clinical sensitivity is not firmly established.

This test provides full coverage of all coding exons of the POMP gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).