Palmoplantar keratoderma and erythrokeratodermas

Gene: RHBDF2

Green List (high evidence)

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

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.