Palmoplantar keratoderma and erythrokeratodermas
Gene: RHBDF2
Gain of function mutations
Very rare, large familiesCreated: 14 Mar 2017, 7:35 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
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.
Promoted to Version 1, April 11th 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for RHBDF2 were set to tylosis with esophageal cancer, 148500; KERATOSIS PALMARIS ET PLANTARIS WITH ESOPHAGEAL CANCER; PALMOPLANTAR KERATODERMA WITH ESOPHAGEAL CANCER; Hyperkeratosis, diffuse palmoplantar (tylosis); Howel-Evans syndrome; Focal keratoderma; tylosis with oesophageal cancer; oral leukokeratosis
Publications for RHBDF2 were set to 22638770; 22265016
Mode of pathogenicity for RHBDF2 was changed to Other - please provide details in the comments
Mode of inheritance for RHBDF2 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Amber List (Moderate Evidence).
Mode of inheritance for RHBDF2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
RHBDF2 was created by rfoulger
RHBDF2 was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Other