Palmoplantar keratoderma and erythrokeratodermas

Gene: KRT6C

Green List (high evidence)

Targeted sequencing through PC Project

Created: 14 Mar 2017, 6:50 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Focal keratoderma; dystrophic nails

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Comment on mode of pathogenicity: Kept mode-of-pathogenicity as 'Other' based on comment from Edel O'Toole: Keratin mutations are generally thought to be dominant negative.

Created: 11 Apr 2017, 1:02 p.m.

Comment on mode of inheritance: Mode of inheritance sourced from OMIM.

Created: 9 Jan 2017, 4:39 p.m.

Comment on list classification: Updated rating from Red to green: Not a confirmed DD gene, but 3 variants listed in OMIM (all from same 2010 publication: PMID:19609311) and KRT6C is listed for Prior genetic testing in the Eligibility statement.

Created: 9 Jan 2017, 4:38 p.m.

In 3 affected members of a Japanese family with focal or diffuse palmoplantar keratoderma (PPKNEFD; OMIM: 615735), Wilson et al. (2010, PMID:19609311) identified heterozygosity for a c.1414G-A transition in exon 7 of the KRT6C gene, resulting in a E472K substitution. The same E472K mutation was found in a father and daughter with focal plantar keratoderma (and not in an unaffected son) by Kubo et al. (2013, PMID:23662636); palmar skin as well as the nails of hands and feet were normal in the affected individuals.

Created: 9 Jan 2017, 4:36 p.m.

In affected members of a 4-generation family with focal palmoplantar keratoderma (PPKNEFD; OMIM:615735), Wilson et al. (2010, PMID:19609311) identified heterozygosity for a 27-bp deletion (c.1384_1410del27) in exon 7 of KRT6C . This mutation resulted in an in-frame deletion (Ile462_Glu470del).

Created: 9 Jan 2017, 4:34 p.m.

In a father and son in 1 family as well as the affected members of an unrelated 4-generation family with focal palmoplantar keratoderma (PPKNEFD; OMIM:615735), Wilson et al. (2010, PMID:19609311) identified heterozygosity for a 3-bp deletion (c.516_518delCAA) in exon 1 of the KRT6C gene, resulting in an in-frame deletion (Asn172del). The mutation segregated with disease in both families; however, the 3-bp deletion was also present in 3 of 335 population controls.

Created: 9 Jan 2017, 4:33 p.m.