Ichthyosis and erythrokeratoderma

Gene: POMP

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 5 Dec 2024, 10:34 p.m. | Last Modified: 5 Dec 2024, 10:34 p.m.

Panel Version: 3.30

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: There is sufficient evidence to support the gene-disease association but based on previous reviews, POMP is currently classified as Red on this panel due the single 1bp deletion identified in all cases to date residing in the 5'UTR of the POMP gene.

The gene rating is conflicting on the R166 Palmoplantar keratodermas, where POMP is rated Green for the same phenotype. This has been tagged for NHSE expert review, and therefore also tagging the association on this panel so that the two panels can be considered together and the overall classification be aligned.

Created: 24 Jan 2024, 5:12 p.m. | Last Modified: 24 Jan 2024, 5:12 p.m.

Panel Version: 3.22

Green List (high evidence)

Comment on list classification: Changed rating from Green to Red after discussion with Emma Baple and Ellen McDonagh, because the known pathogenic variant reported in all cases so far is in the 5'UTR of the POMP gene. Added 'curated variant list' tag, to flag this non-coding variant.

Created: 10 Apr 2017, 12:38 p.m.

Comment on mode of inheritance: Biallelic inheritance confirmed by OMIM and G2P.

Created: 10 Apr 2017, 8:24 a.m.

Added 'promoter' and 'non-coding-known-pathogenic' tags because the variant described in PMID:20226437 and PMID:27503413 is confirmed as pathogenic on ClinVar, and lies in the 5'UTR of the POMP gene.

Created: 3 Apr 2017, 2:03 p.m.

Palmoplantar keratoderma (PPK) is a phenotype of 'Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952 (KLICK syndrome). In 12 patients from 8 unrelated European families (from Spain, Italy, Netherlands, Sweden, Norway) with OMIM:601952, Dahlqvist et al. (2010, PMID: 20226437) identified homozygosity for a 1-bp deletion (-95delC) within a highly conserved 5' region of the POMP gene. Haplotype analysis suggested that the -95delC variant is a recurrent rather than a founder mutation.

Created: 3 Apr 2017, 12:58 p.m.

PMID:27503413 (Morice-Picard, 2017) report a young patient born from related parents, originally from the SW of France. The patient was presenting at birth with palmar keratoderma, and PPK was still present at the age of 11 years. Molecular analysis identified a homozygous 1-bp deletion in the 5′UTR non-coding region of the POMP gene (c.-95delC)- the same variation as reported in 20226437.

Created: 3 Apr 2017, 12:57 p.m.

Comment on list classification: Updated rating from Red to Green after discussion with Helen Brittain: PPK is a key feature of KLICK syndrome, and sufficient cases to support causation (PMID:20226437 and PMID:27503413). Note that all reported cases so far list the same 1bp deletion.

Created: 3 Apr 2017, 12:55 p.m.