Palmoplantar keratoderma and erythrokeratodermas
Gene: KRT6C
Targeted sequencing through PC ProjectCreated: 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.
Promoted to Version 1, April 11th 2017: Reviews were assessed, and panel was revised according to expert review and additional curation.
Mode of pathogenicity for KRT6C was changed to Other - please provide details in the comments
Phenotypes for KRT6C were set to Palmoplantar keratoderma, nonepidermolytic, focal or diffuse, 615735; Focal keratoderma; dystrophic nails
Phenotypes for gene KRT6C were set to Palmoplantar keratoderma, nonepidermolytic, focal or diffuse, 615735
Mode of inheritance for KRT6C was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
Model of inheritance for gene KRT6C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
KRT6C was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Source: Radboud University Medical Center, Nijmegen
KRT6C was created by ellenmcdonagh
KRT6C was added to Palmoplantar keratoderma and erythrokeratodermaspanel. Sources: Eligibility statement prior genetic testing