Ichthyosis and erythrokeratodermaGene: RHBDF2
Gain of function mutations
Very rare, large families
Created: 14 Mar 2017, 7:35 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Focal keratoderma; oesophageal cancer; oral leukokeratosis
Comment on list classification: Updated rating from Amber to Green: One green review plus sufficient cases to support causation of 'Tylosis and esophageal cancer (MIM:148500)' which presents with a PPK phenotype. Confirmed DD-G2P gene for MIM:148500.
Created: 20 Mar 2017, 12:18 p.m.
3 heterozygous RHBDF2 variants (3 unrelated cases) listed in OMIM for 'Tylosis and esophageal cancer' (TOC, OMIM:148500) from two papers: Blaydon et al., 2012 (PMID:22265016) and Saarinen et al., 2012 (PMID:22638770), in UK, US, German and Finnish populations.
Created: 20 Mar 2017, 12:16 p.m.
Comment on mode of pathogenicity: Reviewer notes G.O.F mutations, and Blaydon et al, 2012 (PMID:22265016) suggest altered RHBDF2 represents a gain-of-function allele that results in sustained EGFR signaling within the cells.
Created: 20 Mar 2017, 10:34 a.m.
Comment on list classification: Updated rating from Red to Amber ready for external review. >3 cases of RHBDF2 variants linked to Tylosis and esophageal cancer' (TOC, OMIM:148500) and RHBDF2 is a confirmed DD gene for OMIM:148500.
Created: 10 Jan 2017, 4:40 p.m.
RHBDF2 is a confirmed DD gene for 'Tylosis with esophageal cancer, OMIM:148500)' a disorder where Focal non-epidermolytic palmoplantar keratoderma (PPK) is associated with oesophageal cancer.
Created: 9 Jan 2017, 4:59 p.m.
Comment on mode of inheritance: Mode of inheritance sourced from OMIM.
Created: 5 Jan 2017, 1:22 p.m.
gene: RHBDF2 was added gene: RHBDF2 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: RHBDF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: RHBDF2 were set to 22265016; 22638770 Phenotypes for gene: RHBDF2 were set to Howel-Evans syndrome; tylosis with oesophageal cancer; PALMOPLANTAR KERATODERMA WITH ESOPHAGEAL CANCER; oral leukokeratosis; Focal keratoderma; Hyperkeratosis, diffuse palmoplantar (tylosis); tylosis with esophageal cancer, 148500; KERATOSIS PALMARIS ET PLANTARIS WITH ESOPHAGEAL CANCER Mode of pathogenicity for gene: RHBDF2 was set to Other - please provide details in the comments