Ichthyosis and erythrokeratodermaGene: POMP
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.
Tag promoter tag was added to gene: POMP.
gene: POMP was added gene: POMP was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Red Mode of inheritance for gene: POMP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POMP were set to 27503413; 20226437 Phenotypes for gene: POMP were set to Keratosis linearis with ichthyosis congenita and sclerosing keratoderma, 601952