Palmoplantar keratodermas
Gene: POMPComment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.
PPK is a key feature of KLICK syndrome, and there are sufficient cases to support causation (PMID:20226437 and PMID:27503413). However, the pathogenic variant reported in all cases so far is the same 1bp deletion in the 5'UTR of the POMP gene (c.-95delC). For this reason, it is currently rated as Red on the R165 Ichthyosis and erythrokeratoderma panel (v3.2).
If it is decided that POMP should remain as Green on this panel, it should probably also be promoted to Green status on R165 (also tagged for expert review).
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Supporting evidence (reviews copied from R165 panel):
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.
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: 24 Jan 2024, 4:59 p.m. | Last Modified: 24 Jan 2024, 5:04 p.m.
Panel Version: 3.22
Comment on list classification: Inclusion of this gene on the panel should be reviewed by the NHSE specialist group.
There is sufficient evidence to support a gene-disease association, however the pathogenic variant reported in all cases so far is in the 5'UTR of the POMP gene (c.-95delC). For this reason, it is currently rated as Red on the R165 Ichthyosis and erythrokeratoderma panel (v3.2).
If it is decided that POMP should remain as Green on this panel, it should probably also be promoted to Green status on R165 (also tagged for expert review).
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Supporting evidence (reviews copied from R165 panel):
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.
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: 24 Jan 2024, 4:59 p.m. | Last Modified: 24 Jan 2024, 4:59 p.m.
Panel Version: 3.18
This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted: POMP; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.Created: 28 Jan 2019, 10:47 a.m.
Tag Q1_24_demote_red tag was added to gene: POMP. Tag Q1_24_expert_review tag was added to gene: POMP.
Publications for gene: POMP were set to 27503413; 20226437
Phenotypes for gene: POMP were changed from Keratosis linearis with ichthyosis congenita and sclerosing keratoderma to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, OMIM:601952
Publications for gene: POMP were set to
Gene: pomp has been classified as Green List (High Evidence).
Gene: pomp has been classified as Green List (High Evidence).
Tag promoter tag was added to gene: POMP. Tag non-coding-known-pathogenic tag was added to gene: POMP.
Source London North GLH was added to POMP.
gene: POMP was added gene: POMP was added to Palmoplantar keratodermas. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: POMP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: POMP were set to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma